Co-Infection of ART-treated SIVmac239+ Rhesus Macaques with Plasmodium fragile Results in Elevated Inflammation which Associates with Neutrophil Function

Sydney M Nemphos; Hannah C Green; James E Prusak; Sallie L Fell; Kelly Goff; Megan Varnado; Kaitlin Didier; Natalie Guy; Matilda J Moström; Coty Tatum; Chad Massey; Mary B Barnes; Lori A Rowe; Carolina Allers; Robert V Blair; Monica E Embers; Nicholas J Maness; Preston A Marx; Brooke Grasperge; Amitinder Kaur; Kristina De Paris; Jeffrey G Shaffer; Tiffany Hensley-McBain; Berlin Londono-Renteria; Jennifer A Manuzak

doi:10.20944/preprints202405.1071.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Co-Infection of ART-treated SIVmac239+ Rhesus Macaques with Plasmodium fragile Results in Elevated Inflammation which Associates with Neutrophil Function

Version 1 : Received: 16 May 2024 / Approved: 16 May 2024 / Online: 16 May 2024 (10:07:19 CEST)

How to cite: Nemphos, S. M.; Green, H. C.; Prusak, J. E.; Fell, S. L.; Goff, K.; Varnado, M.; Didier, K.; Guy, N.; Moström, M. J.; Tatum, C.; Massey, C.; Barnes, M. B.; Rowe, L. A.; Allers, C.; Blair, R. V.; Embers, M. E.; Maness, N. J.; Marx, P. A.; Grasperge, B.; Kaur, A.; De Paris, K.; Shaffer, J. G.; Hensley-McBain, T.; Londono-Renteria, B.; Manuzak, J. A. Co-Infection of ART-treated SIVmac239+ Rhesus Macaques with Plasmodium fragile Results in Elevated Inflammation which Associates with Neutrophil Function. Preprints 2024, 2024051071. https://doi.org/10.20944/preprints202405.1071.v1 Nemphos, S. M.; Green, H. C.; Prusak, J. E.; Fell, S. L.; Goff, K.; Varnado, M.; Didier, K.; Guy, N.; Moström, M. J.; Tatum, C.; Massey, C.; Barnes, M. B.; Rowe, L. A.; Allers, C.; Blair, R. V.; Embers, M. E.; Maness, N. J.; Marx, P. A.; Grasperge, B.; Kaur, A.; De Paris, K.; Shaffer, J. G.; Hensley-McBain, T.; Londono-Renteria, B.; Manuzak, J. A. Co-Infection of ART-treated SIVmac239+ Rhesus Macaques with Plasmodium fragile Results in Elevated Inflammation which Associates with Neutrophil Function. Preprints 2024, 2024051071. https://doi.org/10.20944/preprints202405.1071.v1

Abstract

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. Here, we used the rhesus macaque (RM) model to characterize the immunopathogenic impact of Plasmodium fragile co-infection during antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)-infection. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VL) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines linked with neutrophil function, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was 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 neutrophil functionality during co-infection. Finally, we characterized 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 data indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

Keywords

NHP; P. fragile; SIV; malaria; neutrophils; co-infection; immunology

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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