{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:47:03Z","timestamp":1790146023342,"version":"4.0.1"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammation has a role in the pathogenesis of childhood malnutrition. We investigated the effect of malnutrition and inflammatory challenge on bone marrow composition and bone health. We studied an established murine model of moderate acute malnutrition at baseline and after acute inflammatory challenge with bacterial lipopolysaccharide (LPS), a surrogate of Gram-negative bacterial sepsis, or <jats:italic>Leishmania donovani<\/jats:italic>, the cause of visceral leishmaniasis. Both of these infections cause significant morbidity and mortality in malnourished children. Of the 2 stimuli, LPS caused more pronounced bone marrow changes that were amplified in malnourished mice. LPS challenge led to increased inflammatory cytokine expression (<jats:italic>Il1b<\/jats:italic>, <jats:italic>Il6<\/jats:italic>, and <jats:italic>Tnf<\/jats:italic>), inflammasome activation, and inflammatory monocyte accumulation in the bone marrow of malnourished mice. Depletion of inflammatory monocytes in <jats:italic>Csfr1<\/jats:italic>-LysMcre-DT malnourished mice significantly reduced the inflammasome activation and IL1-\u00df production after LPS challenge. The inflammatory challenge also led to increased expansion of mesenchymal stem cells (MSCs), bone marrow adiposity, and expression of genes (<jats:italic>Pparg<\/jats:italic>, <jats:italic>Adipoq<\/jats:italic>, and <jats:italic>Srbp1<\/jats:italic>) associated with adipogenesis in malnourished mice. This suggests that inflammatory challenge promotes differentiation of BM MSCs toward the adipocyte lineage rather than toward bone-forming osteoblasts in the malnourished host. Concurrent with this reduced osteoblastic potential there was an increase in bone-resorbing osteoclasts, enhanced osteoclast activity, upregulation of inflammatory genes, and IL-1B involved in osteoclast differentiation and activation. The resulting weakened bone formation and increased bone resorption would contribute to the bone fragility associated with malnutrition. Lastly, we evaluated the effect of replacing lipid rich in omega-6 fatty acids (corn oil) with lipid-rich in omega-3 fatty acids (fish oil) in the nutrient-deficient diet. LPS-challenged malnourished mice that received dietary fish oil showed decreased expression of inflammatory cytokines and <jats:italic>Rankl<\/jats:italic> and reduced osteoclast differentiation and activation in the bone marrow. This work demonstrates that the negative effect of inflammatory challenge on bone marrow is amplified in the malnourished host. Increasing dietary intake of omega-3 fatty acids may be a means to reduce inflammation and improve bone health in malnourished children.<\/jats:p>","DOI":"10.3389\/fimmu.2022.846246","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T04:38:12Z","timestamp":1659415092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Inflammatory stimuli alter bone marrow composition and compromise bone health in the malnourished host"],"prefix":"10.3389","volume":"13","author":[{"given":"E. Yaneth","family":"Osorio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Gugala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace T.","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genesis","family":"Palacios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Cordova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashanti","family":"Uscanga-Palomeque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno L.","family":"Travi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Melby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/112.10.1974","article-title":"The effect of severe protein deficiency on serum zinc concentration of mice fed a requirement level or a very high level of dietary zinc","volume":"112","author":"Filteau","year":"1982","journal-title":"J Nutr"},{"key":"B2","article-title":"Understanding zinc: recent observations and interpretations","volume":"124","author":"Sandstead","year":"1994","journal-title":"J Lab Clin Med"},{"key":"B3","volume-title":"Levels and trends in child malnutrition: key findings of the 2021 edition of the joint child malnutrition estimates","year":"2021"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61690-0","article-title":"Maternal and child undernutrition: global and regional exposures and health consequences","volume":"371","author":"Black","year":"2008","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002934","article-title":"Mortality and recovery following moderate and severe acute malnutrition in children aged 6-18 months in rural jharkhand and odisha, eastern India: A cohort study","volume":"16","author":"Prost","year":"2019","journal-title":"PloS Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2018.07.007","article-title":"New insights into the pathogenesis and treatment of malnutrition","volume":"47","author":"Thaxton","year":"2018","journal-title":"Gastroenterol Clin North Am"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-4018","article-title":"Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality","volume":"99","author":"Bartz","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","first-page":"17067","DOI":"10.1038\/nrdp.2017.67","article-title":"Severe childhood malnutrition","volume":"3","author":"Bhutta","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1017\/s0029665106005192","article-title":"Nutrition and bone growth and development","volume":"65","author":"Prentice","year":"2006","journal-title":"Proc Nutr Soc"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.20-0963","article-title":"Environmental, metabolic, and inflammatory factors converge in the pathogenesis of moderate acute malnutrition in children: An observational cohort study","volume":"4","author":"Patterson","year":"2021","journal-title":"Am J Trop Med Hygiene"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.846155","article-title":"Pathologic in!ammation in malnutrition is driven by proin!ammatory intestinal microbiota, Large intestine barrier dysfunction, and translocation of bacterial lipopolysaccharide","volume":"13","author":"Patterson","year":"2022","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00119-16","article-title":"Impact of childhood malnutrition on host defense and infection","volume":"30","author":"Ibrahim","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn099","article-title":"Multi-country analysis of the effects of diarrhoea on childhood stunting","volume":"37","author":"Checkley","year":"2008","journal-title":"Int J Epidemiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(21)00133-4","article-title":"Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe","volume":"5","author":"Rukuni","year":"2021","journal-title":"Lancet Child Adolesc Health"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000070","article-title":"Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life","volume":"28","author":"Yin","year":"2014","journal-title":"AIDS"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268800051074","article-title":"Serological diagnosis of leishmaniasis: on detecting infection as well as disease","volume":"110","author":"Dye","year":"1993","journal-title":"Epidemiol Infect"},{"key":"B17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/tmi.12407","article-title":"Clinical aspects of paediatric visceral leishmaniasis in north-west Ethiopia","volume":"20","author":"Diro","year":"2015","journal-title":"Trop Med Int Health TM IH"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4103\/jfmpc.jfmpc_2411_20","article-title":"Effects of vitamin d on bone density in healthy children: A systematic review","volume":"11","author":"Karimian","year":"2022","journal-title":"J Family Med Prim Care"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058872","article-title":"Protein malnutrition induces bone marrow mesenchymal stem cells commitment to adipogenic differentiation leading to hematopoietic failure","volume":"8","author":"Cunha","year":"2013","journal-title":"PloS One"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/628740","article-title":"Evidence for the adverse effect of starvation on bone quality: a review of the literature","volume":"2015","author":"Kueper","year":"2015","journal-title":"Int J Endocrinol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12718","article-title":"Clinical implications of bone marrow adiposity","volume":"283","author":"Veldhuis-Vlug","year":"2018","journal-title":"J Intern Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733","article-title":"Monocyte and macrophage heterogeneity","volume":"5","author":"Gordon","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1170540","article-title":"In vivo analysis of dendritic cell development and homeostasis","volume":"324","author":"Liu","year":"2009","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81569-x","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02925","article-title":"TNF-\u03b1 directly enhances osteocyte RANKL expression and promotes osteoclast formation","volume":"10","author":"Marahleh","year":"2019","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80209-3","article-title":"Osteoprotegerin: a novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2004.06.004","article-title":"The molecular triad OPG\/RANK\/RANKL: involvement in the orchestration of pathophysiological bone remodeling","volume":"15","author":"Theoleyre","year":"2004","journal-title":"Cytokine Growth Factor Rev"},{"key":"B28","doi-asserted-by":"publisher","first-page":"6630","DOI":"10.1038\/s41598-017-07014-0","article-title":"Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation","volume":"7","author":"Alippe","year":"2017","journal-title":"Sci Rep"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/iai.68.8.4681-4687.2000","article-title":"Toll-like receptor 4-deficient mice have reduced bone destruction following mixed anaerobic infection","volume":"68","author":"Hou","year":"2000","journal-title":"Infect Immun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/iai.70.6.3143-3148.2002","article-title":"Bacteria induce osteoclastogenesis via an osteoblast-independent pathway","volume":"70","author":"Jiang","year":"2002","journal-title":"Infect Immun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.12.1741","article-title":"Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-fms and receptor activator of nuclear factor kappaB (RANK) receptors","volume":"190","author":"Arai","year":"1999","journal-title":"J Exp Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01408","article-title":"Immune function and diversity of osteoclasts in normal and pathological conditions","volume":"10","author":"Madel","year":"2019","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.216267","article-title":"Common signalling pathways in macrophage and osteoclast multinucleation","volume":"131","author":"Pereira","year":"2018","journal-title":"J Cell Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s12891-015-0664-5","article-title":"Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis","volume":"16","author":"Prieto-Potin","year":"2015","journal-title":"BMC Musculoskelet Disord"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.7260","article-title":"Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells","volume":"87","author":"Udagawa","year":"1990","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B36","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s12020-012-9813-x","article-title":"Osteoporosis in chronic inflammatory disease: the role of malnutrition","volume":"43","author":"Montalcini","year":"2013","journal-title":"Endocrine"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0203064jlb.0203064","article-title":"Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-kappaB activation, and nitric oxide production","volume":"74","author":"Anstead","year":"2003","journal-title":"J Leukoc Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.8.4709-4718.2001","article-title":"Malnutrition alters the innate immune response and increases early visceralization following leishmania donovani infection","volume":"69","author":"Anstead","year":"2001","journal-title":"Infect Immun"},{"key":"B39","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.plefa.2009.04.011","article-title":"Malnutrition promotes prostaglandin over leukotriene production and dysregulates eicosanoid-cytokine crosstalk in activated resident macrophages","volume":"81","author":"Anstead","year":"2009","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002329","article-title":"The malnutrition-related increase in early visceralization of leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow","volume":"7","author":"Ibrahim","year":"2013","journal-title":"PloS Negl Trop Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01778-14","article-title":"Deficiency of lymph node-resident dendritic cells (DCs) and dysregulation of DC chemoattractants in a malnourished mouse model of leishmania donovani infection","volume":"82","author":"Ibrahim","year":"2014","journal-title":"Infect Immun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2016.021","article-title":"Current murine models of sepsis","volume":"17","author":"Lewis","year":"2016","journal-title":"Surg Infect (Larchmt)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-6-160","article-title":"Bacteraemia among severely malnourished children infected and uninfected with the human immunodeficiency virus-1 in Kampala, Uganda","volume":"6","author":"Bachou","year":"2006","journal-title":"BMC Infect Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1056\/NEJMoa040275","article-title":"Bacteremia among children admitted to a rural hospital in Kenya","volume":"352","author":"Berkley","year":"2005","journal-title":"New Engl J Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068699","article-title":"Infections in children admitted with complicated severe acute malnutrition in Niger","volume":"8","author":"Page","year":"2013","journal-title":"PloS One"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/156.6.1030","article-title":"Malnutrition as a risk factor for severe visceral leishmaniasis","volume":"156","author":"Cerf","year":"1987","journal-title":"J Infect Dis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2009.01117.x","article-title":"Protein-energy malnutrition as a risk factor for visceral leishmaniasis: a review","volume":"31","author":"Malafaia","year":"2009","journal-title":"Parasite Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2019.110712","article-title":"Nutrition, malnutrition, and leishmaniasis","volume":"73","author":"Nweze","year":"2020","journal-title":"Nutrition"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130903","article-title":"Intestinal monocytes and macrophages are required for T cell polarization in response to citrobacter rodentium","volume":"210","author":"Schreiber","year":"2013","journal-title":"J Exp Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22012","article-title":"A novel Ly6C\/Ly6G-based strategy to analyze the mouse splenic myeloid compartment","volume":"81","author":"Rose","year":"2012","journal-title":"Cytomet A"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2014.07.262","article-title":"Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment","volume":"42","author":"Kuzmac","year":"2014","journal-title":"Exp Hematol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02567","article-title":"A novel reliable and efficient procedure for purification of mature osteoclasts allowing functional assays in mouse cells","volume":"9","author":"Madel","year":"2018","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.bone.2018.05.019","article-title":"Defining osteoblast and adipocyte lineages in the bone marrow","volume":"118","author":"Pierce","year":"2019","journal-title":"Bone"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-264804","article-title":"NLRP3 mediates osteolysis through inflammation-dependent and -independent mechanisms","volume":"29","author":"Qu","year":"2015","journal-title":"FASEB J"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1210\/endo-124-5-2172","article-title":"Parathyroid hormone-related protein and interleukin-1 alpha synergistically stimulate bone resorption in vitro and increase the serum calcium concentration in mice in vivo","volume":"124","author":"Sato","year":"1989","journal-title":"Endocrinology"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182096","article-title":"Lipid based nutrient supplements (LNS) for treatment of children (6 months to 59 months) with moderate acute malnutrition (MAM): A systematic review","volume":"12","author":"Gera","year":"2017","journal-title":"PloS One"},{"key":"B59","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s12916-015-0315-6","article-title":"Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial","volume":"13","author":"Jones","year":"2015","journal-title":"BMC Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.04.049","article-title":"Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance - a review","volume":"203","author":"Saini","year":"2018","journal-title":"Life Sci"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.08.010","article-title":"Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance","volume":"1851","author":"Calder","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/nu8030128","article-title":"An increase in the omega-6\/Omega-3 fatty acid ratio increases the risk for obesity","volume":"8","author":"Simopoulos","year":"2016","journal-title":"Nutrients"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S45263","article-title":"Endogenous n-3 polyunsaturated fatty acids (PUFAs) mitigate ovariectomy-induced bone loss by attenuating bone marrow adipogenesis in FAT1 transgenic mice","volume":"7","author":"Chen","year":"2013","journal-title":"Drug Des Devel Ther"},{"key":"B64","doi-asserted-by":"publisher","first-page":"10364","DOI":"10.1038\/s41598-021-89827-8","article-title":"Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL\/6 mice and in vitro studies","volume":"11","author":"Cugno","year":"2021","journal-title":"Sci Rep"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1172\/jci19900","article-title":"PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors","volume":"113","author":"Akune","year":"2004","journal-title":"J Clin Invest"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.08.006","article-title":"PPAR\u03b3 in bone homeostasis","volume":"21","author":"Wan","year":"2010","journal-title":"Trends Endocrinol Metab"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-019-01231-1","article-title":"Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors","volume":"68","author":"Korbecki","year":"2019","journal-title":"Inflammation Res"},{"key":"B68","article-title":"Prostaglandin E2 is raised in kwashiorkor","volume":"92","author":"Iputo","year":"2002","journal-title":"S Afr Med J"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.10.001","article-title":"Effects of bioactive lipids and lipoproteins on bone","volume":"25","author":"Tintut","year":"2014","journal-title":"Trends Endocrinol Metab"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2019.108337","article-title":"Atherogenic diet-induced bone loss is primarily due to increased osteoclastogenesis in mice","volume":"79","author":"Sul","year":"2020","journal-title":"J Nutr Biochem"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.09.010","article-title":"Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging","volume":"18","author":"Youm","year":"2013","journal-title":"Cell Metab"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.3390\/cells9102157","article-title":"Multitasking by the OC lineage during bone infection: Bone resorption, immune modulation, and microbial niche","volume":"9","author":"Roper","year":"2020","journal-title":"Cells"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00694","article-title":"Bone marrow fat and hematopoiesis","volume":"9","author":"Wang","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/nature08099","article-title":"Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment","volume":"460","author":"Naveiras","year":"2009","journal-title":"Nature"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701959","article-title":"Metabolic changes in malnutrition","volume":"19","author":"Emery","year":"2005","journal-title":"Eye (Lond)"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.578194","article-title":"Dual effects of lipid metabolism on osteoblast function","volume":"11","author":"Alekos","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B78","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1093\/intimm\/dxz063","article-title":"IgG immune complexes with staphylococcus aureus protein a enhance osteoclast differentiation and bone resorption by stimulating fc receptors and TLR2","volume":"32","author":"Kamohara","year":"2020","journal-title":"Int Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200005000-00006","article-title":"Pathogenesis of bone erosions in rheumatoid arthritis","volume":"12","author":"Goldring","year":"2000","journal-title":"Curr Opin Rheumatol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.063016-0","article-title":"Staphylococcus aureus protein a binding to osteoblast tumour necrosis factor receptor 1 results in activation of nuclear factor kappa b and release of interleukin-6 in bone infection","volume":"159","author":"Claro","year":"2013","journal-title":"Microbiol (Reading)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/2049-632x.12082","article-title":"Mycobacterium tuberculosis escapes from the phagosomes of infected human osteoclasts reprograms osteoclast development via dysregulation of cytokines and chemokines","volume":"70","author":"Hoshino","year":"2014","journal-title":"Pathog Dis"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038500","article-title":"Infection of RANKL-primed RAW-d macrophages with porphyromonas gingivalis promotes osteoclastogenesis in a TNF-\u03b1-independent manner","volume":"7","author":"Kukita","year":"2012","journal-title":"PloS One"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526037","article-title":"Regulation of the leishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1","volume":"35","author":"Forget","year":"2005","journal-title":"Eur J Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1128\/CMR.18.2.293-305.2005","article-title":"Subversion mechanisms by which leishmania parasites can escape the host immune response: a signaling point of view","volume":"18","author":"Olivier","year":"2005","journal-title":"Clin Microbiol Rev"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001198","article-title":"Evidence that lipopolisaccharide may contribute to the cytokine storm and cellular activation in patients with visceral leishmaniasis","volume":"5","author":"Santos-Oliveira","year":"2011","journal-title":"PloS Negl Trop Dis"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2006.02.007","article-title":"Experimental model of chronic osteomyelitis caused by leishmania (L) amazonensis","volume":"98","author":"Costa","year":"2006","journal-title":"Acta Trop"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00511","article-title":"Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond","volume":"5","author":"Walsh","year":"2014","journal-title":"Front Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900729","article-title":"A critical role for hemolysins and bacterial lipoproteins in staphylococcus aureus-induced activation of the Nlrp3 inflammasome","volume":"183","author":"Mu\u00f1oz-Planillo","year":"2009","journal-title":"J Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035979","article-title":"Constitutively activated NLRP3 inflammasome causes inflammation and abnormal skeletal development in mice","volume":"7","author":"Bonar","year":"2012","journal-title":"PloS One"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2016.02.016","article-title":"Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice","volume":"32","author":"Figueiredo","year":"2016","journal-title":"Nutrition"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/s0753-3322(02)00253-6","article-title":"The importance of the ratio of omega-6\/omega-3 essential fatty acids","volume":"56","author":"Simopoulos","year":"2002","journal-title":"BioMed Pharmacother"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4724fje","article-title":"RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis","volume":"20","author":"Hasturk","year":"2006","journal-title":"FASEB J"},{"key":"B93","doi-asserted-by":"publisher","first-page":"298","DOI":"10.2334\/josnusd.19-0267","article-title":"Inhibitory effect of omega-3 fatty acids on alveolar bone resorption and osteoclast differentiation","volume":"62","author":"Ozaki","year":"2020","journal-title":"J Oral Sci"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/s0952-3278(03)00063-2","article-title":"Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism","volume":"68","author":"Watkins","year":"2003","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"B95","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12916-015-0352-1","article-title":"Balancing omega-6 and omega-3 fatty acids in ready-to-use therapeutic foods (RUTF)","volume":"13","author":"Brenna","year":"2015","journal-title":"BMC Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.846246\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T04:38:23Z","timestamp":1659415103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.846246\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":95,"alternative-id":["10.3389\/fimmu.2022.846246"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.846246","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]},"article-number":"846246"}}