{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:22:52Z","timestamp":1760232172667,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Signal regulatory protein \u03b1 (SIRP\u03b1) is an immunoreceptor expressed in myeloid innate immune cells that signals for inhibition of both phagocytosis and inflammatory response. Malaria parasites have evolutionarily selected multiple mechanisms that allow them to evade host immune defenses, including the modulation of cells belonging to innate immunity. Notwithstanding, little attention has been given to SIRP\u03b1 in the context of immunosuppressive states induced by malaria. The present study attempted to investigate if malaria parasites are endowed with the capacity of modulating the expression of SIRP\u03b1 on cells of innate immune system. Human peripheral blood mononuclear cells (PBMC) from healthy individuals were incubated in the presence of lipopolysaccharide (LPS) or crude extracts of P. falciparum or P. vivax and then, the expression of SIRP\u03b1 was evaluated by flow cytometry. As expected, LPS showed an inhibitory effect on the expression of SIRP\u03b1 in the population of monocytes, characterized by cell morphology in flow cytometry analysis, while Plasmodium extracts induced a significant positive modulation. Additional phenotyping of cells revealed that the modulatory potential of Plasmodium antigens on SIRP\u03b1 expression was restricted to the population of monocytes (CD14+CD11c+), as no effect on myeloid dendritic cells (CD14\u2212CD11c+) was observed. We hypothesize that malaria parasites explore inhibitory signaling of SIRP\u03b1 to suppress antiparasitic immune responses contributing to the establishment of infection. Nevertheless, further studies are still required to better understand the role of SIRP\u03b1 modulation in malaria immunity and pathogenesis.<\/jats:p>","DOI":"10.3390\/microorganisms10050903","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T02:14:39Z","timestamp":1650939279000},"page":"903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Signal Regulatory Protein \u03b1 (SIRP\u03b1) by Plasmodium Antigenic Extract: A Preliminary In Vitro Study on Peripheral Blood Mononuclear Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7095-1624","authenticated-orcid":false,"given":"Priscilla da Costa","family":"Martins","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-2898","authenticated-orcid":false,"given":"Hugo Amorim dos Santos","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9354-3682","authenticated-orcid":false,"given":"Carolina Moreira","family":"Blanco","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luana","family":"Santos-de-Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian Rose","family":"Pratt-Riccio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udio Tadeu","family":"Daniel-Ribeiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo Renato Rivas","family":"Totino","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1586\/erv.11.189","article-title":"Pattern recognition receptors: Sentinels in innate immunity and targets of new vaccine adjuvants","volume":"11","author":"Olive","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.molimm.2003.10.005","article-title":"Innate immunity: An overview","volume":"40","author":"Beutler","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00436-006-0306-9","article-title":"Subversion of innate and adaptive immune responses by Toxoplasma gondii","volume":"100","author":"Lang","year":"2007","journal-title":"Parasitol. Res."},{"key":"ref_4","first-page":"463","article-title":"Malaria parasites: The great escape","volume":"7","author":"Goh","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mib.2005.12.003","article-title":"Ehrlichia subversion of host innate responses","volume":"9","author":"Rikihisa","year":"2006","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1128\/IAI.00095-07","article-title":"Inhibition of dendritic cell maturation by malaria is dose dependent and does not require Plasmodium falciparum erythrocyte membrane protein 1","volume":"75","author":"Elliott","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/jbiol34","article-title":"Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function","volume":"5","author":"Millington","year":"2006","journal-title":"J. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/21900","article-title":"Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells","volume":"400","author":"Urban","year":"1999","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1046\/j.1365-3024.1997.d01-188.x","article-title":"Plasmodium falciparum malaria blood stage parasites preferentially inhibit macrophages with high phagocytic activity","volume":"19","author":"Leitner","year":"1997","journal-title":"Parasite Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00447-17","DOI":"10.1128\/IAI.00447-17","article-title":"Plasmodium falciparum PfEMP1 modulates monocyte\/macrophage transcription factor activation and cytokine and chemokine responses","volume":"86","author":"Sampaio","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1128\/IAI.66.4.1601-1606.1998","article-title":"Phagocytosis of the malarial pigment, hemozoin, impairs expression of major histocompatibility complex class II antigen, CD54, and CD11c in human monocytes","volume":"66","author":"Schwarzer","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0925-4439(96)00021-X","article-title":"Phagocytosis of malarial pigment hemozoin inhibits NADPH-oxidase activity in human monocyte-derived macrophages","volume":"1316","author":"Schwarzer","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1128\/IAI.73.4.1986-1994.2005","article-title":"Fatal Plasmodium falciparum malaria causes specific patterns of splenic architectural disorganization","volume":"73","author":"Urban","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7788","DOI":"10.4049\/jimmunol.175.12.7788","article-title":"A nomenclature for signal regulatory protein family members","volume":"175","author":"Colonna","year":"2005","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-065X.2008.00666.x","article-title":"Immunoreceptor tyrosine-based inhibition motifs: A quest in the past and future","volume":"224","author":"Jaeger","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0092-8674(03)00758-X","article-title":"By binding SIRPalpha or calreticulin\/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation","volume":"115","author":"Gardai","year":"2003","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1164\/rccm.200711-1661OC","article-title":"Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha","volume":"178","author":"Janssen","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.4049\/jimmunol.167.5.2547","article-title":"Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: Down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation","volume":"167","author":"Latour","year":"2001","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1182\/blood-2002-11-3596","article-title":"A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes","volume":"102","author":"Smith","year":"2003","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"ref_21","unstructured":"Moll, K., Kaneko, A., Scherf, A., and Wahlgren, M. (2013). Methods in Malaria Research, MR4\/ATCC."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1086\/654815","article-title":"On the cytoadhesion of Plasmodium vivax-infected erythrocytes","volume":"202","author":"Carvalho","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/eji.1830200626","article-title":"Human T cell proliferative responses to Plasmodium vivax antigens: Evidence of immunosuppression following prolonged exposure to endemic malaria","volume":"20","author":"Goonewardene","year":"1990","journal-title":"Eur. J. Immunol."},{"key":"ref_24","first-page":"17","article-title":"Cellular immune responses to Plasmodium falciparum antigens in Gambian children during and after an acute attack of falciparum malaria","volume":"73","author":"Riley","year":"1988","journal-title":"Clin. Exp. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1699-0463.1990.tb01051.x","article-title":"Immunosuppression in murine malaria: Suppressor role of macrophages and their products during acute and chronic Plasmodium berghei infection","volume":"98","author":"Wangoo","year":"1990","journal-title":"APMIS"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00651","DOI":"10.1002\/mbo3.651","article-title":"Hemozoin-induced activation of human monocytes toward M2-like phenotype is partially reversed by antimalarial drugs-chloroquine and artemisinin","volume":"8","author":"Bobade","year":"2019","journal-title":"MicrobiologyOpen"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.jinf.2018.09.005","article-title":"Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells","volume":"77","author":"Vallejo","year":"2018","journal-title":"J. Infect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.3389\/fimmu.2017.01814","article-title":"Detection of signal regulatory protein \u03b1 in Saimiri sciureus (Squirrel Monkey) by anti-human monoclonal antibody","volume":"8","author":"Souza","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1084\/jem.20062611","article-title":"LPS-induced down-regulation of signal regulatory protein \u03b1 contributes to innate immune activation in macrophages","volume":"204","author":"Kong","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1183850","DOI":"10.1080\/2162402X.2016.1183850","article-title":"Inhibition of SIRP\u03b1 in dendritic cells potentiates potent antitumor immunity","volume":"5","author":"Liu","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1016\/j.molimm.2008.03.012","article-title":"Signal regulatory protein alpha negatively regulates both TLR3 and cytoplasmic pathways in type I interferon induction","volume":"45","author":"Dong","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1128\/IAI.00718-12","article-title":"Involvement of signal regulatory protein \u03b1, a negative regulator of Toll-like receptor signaling, in impairing the MyD88-independent pathway and intracellular killing of Burkholderia pseudomallei-infected mouse macrophages","volume":"80","author":"Baral","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"31113","DOI":"10.1074\/jbc.M115.682914","article-title":"Cleavage of signal regulatory protein \u03b1 (SIRP\u03b1) enhances inflammatory signaling","volume":"290","author":"Londino","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Burel, J.G., Apte, S.H., McCarthy, J.S., and Doolan, D.L. (2016). Plasmodium vivax but not Plasmodiumfalciparum blood-stage infection in humans is associated with the expansion of a CD8+ T cell population with cytotoxic potential. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005031"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Goncalves, R.M., Scopel, K.K.G., Bastos, M.S., and Ferreira, M.U. (2012). Cytokine balance in human malaria: Does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044394"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.it.2017.12.005","article-title":"SIRP\u03b1-CD47 immune checkpoint blockade in anticancer therapy","volume":"39","author":"Veillette","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1128\/IAI.01426-15","article-title":"CD47-SIRP\u03b1 interactions regulate macrophage uptake of Plasmodium falciparum-infected erythrocytes and clearance of malaria in vivo","volume":"84","author":"Ayi","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/s41590-020-0673-x","article-title":"Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis","volume":"21","author":"Roquilly","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.semcdb.2015.05.004","article-title":"Human mononuclear phagocyte system reunited","volume":"41","author":"Haniffa","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1128\/IAI.72.8.4480-4485.2004","article-title":"Helicobacter pylori induces apoptosis of human monocytes but not monocyte-derived dendritic cells: Role of the cag pathogenicity island","volume":"72","author":"Galgani","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3109\/08830185.2015.1015718","article-title":"Distinct strategies employed by dendritic cells and macrophages in restricting Mycobacterium tuberculosis infection: Different philosophies but same desire","volume":"35","author":"Khan","year":"2016","journal-title":"Int. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1128\/CVI.00282-12","article-title":"Differential interleukin-10 (IL-10) and IL-23 production by human blood monocytes and dendritic cells in response to commensal enteric bacteria","volume":"19","author":"Manuzak","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1046\/j.1365-2567.2003.01557.x","article-title":"Differential response of bovine monocyte-derived macrophages and dendritic cells to infection with Salmonella typhimurium in a low-dose model in vitro","volume":"108","author":"Norimatsu","year":"2003","journal-title":"Immunology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/jlb.58.1.23","article-title":"Role of macrophage-derived nitric oxide in suppression of lymphocyte proliferation during blood-stage malaria","volume":"58","author":"Ahvazi","year":"1995","journal-title":"J. Leukoc. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1475-2875-11-104","article-title":"Plasmodium yoelii blood-stage primes macrophage-mediated innate immune response through modulation of toll-like receptor signaling","volume":"11","author":"Fu","year":"2012","journal-title":"Malar. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1475-2875-7-88","article-title":"Interactions between dendritic cells and CD4+ T cells during Plasmodium infection","volume":"7","author":"Rodriguez","year":"2008","journal-title":"Malar. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1128\/IAI.00820-12","article-title":"Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection","volume":"80","author":"Sponaas","year":"2012","journal-title":"Infect. Immun."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/5\/903\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:01Z","timestamp":1760137261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/5\/903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["microorganisms10050903"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10050903","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2022,4,26]]}}}