{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:14:17Z","timestamp":1760145257810,"version":"build-2065373602"},"reference-count":138,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"J.A.M.","award":["R21OD031435","P51OD011104","U42OD010568","U42OD024282"],"award-info":[{"award-number":["R21OD031435","P51OD011104","U42OD010568","U42OD024282"]}]},{"name":"TNPRC (RRID:SCR_008167) NIH","award":["R21OD031435","P51OD011104","U42OD010568","U42OD024282"],"award-info":[{"award-number":["R21OD031435","P51OD011104","U42OD010568","U42OD024282"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV\/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV\/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV\/P. fragile co-infection pathogenesis.<\/jats:p>","DOI":"10.3390\/v16071036","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T08:57:50Z","timestamp":1719478670000},"page":"1036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elevated Inflammation Associated with Markers of Neutrophil Function and Gastrointestinal Disruption in Pilot Study of Plasmodium fragile Co-Infection of ART-Treated SIVmac239+ Rhesus Macaques"],"prefix":"10.3390","volume":"16","author":[{"given":"Sydney M.","family":"Nemphos","sequence":"first","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah C.","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Prusak","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sallie L.","family":"Fell","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Goff","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Varnado","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlin","family":"Didier","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Guy","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-6638","authenticated-orcid":false,"given":"Matilda J.","family":"Mostr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coty","family":"Tatum","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad","family":"Massey","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary B.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-496X","authenticated-orcid":false,"given":"Lori A.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Allers","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-9414","authenticated-orcid":false,"given":"Robert V.","family":"Blair","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4051-7592","authenticated-orcid":false,"given":"Monica E.","family":"Embers","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9332-7891","authenticated-orcid":false,"given":"Nicholas J.","family":"Maness","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston A.","family":"Marx","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"},{"name":"Department of Tropical Medicine and Infectious Disease, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke","family":"Grasperge","sequence":"additional","affiliation":[{"name":"Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-4896","authenticated-orcid":false,"given":"Amitinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"De Paris","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27559, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3941-3772","authenticated-orcid":false,"given":"Jeffrey G.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-5622","authenticated-orcid":false,"given":"Tiffany","family":"Hensley-McBain","sequence":"additional","affiliation":[{"name":"McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT 59405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-5274","authenticated-orcid":false,"given":"Berlin","family":"Londono-Renteria","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine and Infectious Disease, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-2306","authenticated-orcid":false,"given":"Jennifer A.","family":"Manuzak","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"},{"name":"Department of Tropical Medicine and Infectious Disease, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). 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