T-cell activation, senescence, and exhaustion in asymptomatic HIV/Leish mania infantum co-infection.

Autor:	de Oliveira Mendes-Aguiar C; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil., do Monte Alves M; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Department of Infectious Disease, Health Science Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Health Graduate Program, Federal University of Rio Grande do Norte, Natal, RN, Brazil., de Albuquerque Lopes Machado A; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil., de Góis Monteiro GR; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Medeiros IM; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Department of Infectious Disease, Health Science Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Queiroz JW; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Lima ID; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; State of Rio Grande do Norte Health Secretariat, Natal, RN, Brazil., Pearson RD; Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, USA., Wilson ME; Departments of Internal Medicine and Microbiology & Immunology, University of Iowa and the Veterans' Affairs Medical Center, Iowa City, IA, USA., Glesby MJ; Division of Infectious Disease, Weill Cornell Medical College, New York, NY, USA., do Nascimento ELT; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Department of Infectious Disease, Health Science Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Jerônimo SMB; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Institute of Science and Technology of Tropical Diseases, Natal, RN, Brazil.; Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Mar 06. Date of Electronic Publication: 2023 Mar 06.
DOI:	10.1101/2023.03.06.23286828
Abstrakt:	Background: Leishmania infantum is an opportunistic parasitic infection. An immunocompromised state increases the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL), which has a ~5% fatality rate even with treatment. HIV coinfection increases the risk of death from VL. Methods: A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in HIV positive subjects residing in the state of Rio Grande do Norte, Brazil (n=1,372) and of these a subgroup of subjects were followed longitudinally. Subsequent incident cases of VL were ascertained from a public health database through 2018. A subgroup (n=69) of the cross-sectional study subjects was chosen to assess immune status (T cell activation, senescence, exhaustion) and outcome. The data were compared between asymptomatic HIV+/ L. infantum + (HIV/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response - Leishmanin skin test), AIDS/VL, HIV+ only (HIV+), and Non-HIV/Non L. infantum infection (control subjects). Results: The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgG Leishmania antibodies. After 3 years, 2.4% (8 of 333) of these HIV/Leish coinfected subjects developed AIDS/VL, whereas 1.05% (11 of 1,039) of HIV subjects with negative leishmania serology developed AIDS/VL. Poor adherence to antiretroviral therapy (p=0.0008) or prior opportunistic infections (p=0.0007) was associated with development of AIDS/VL. CD4+ (p=0.29) and CD8+ (p=0.38) T cells counts or viral load (p=0.34) were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8 + CD38 + HLA-DR + T cells were higher in asymptomatic HIV/Leish than HIV group. Likewise, senescent (CD57+) or exhausted (PD1 + ) CD8 + T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups. Conclusion: Although asymptomatic HIV/Leish subjects had normal and similar CD4+ and CD8+ T cells counts, their CD8 + T cells had increased activation, senescence, and exhaustion, which could contribute to risk of developing VL.
Databáze:	MEDLINE
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