Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection.
Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.
Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
Fengliang
F
Liu
Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
Xiuzhen
X
Fan
Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
Sarah
S
Auclair
Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
Monique
M
Ferguson
Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
Jiaren
J
Sun
Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
Lynn
L
Soong
School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
Wei
W
Hou
Institute of Human Virology and Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Robert R
RR
Redfield
U.S. Military HIV Research Program, Water Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Deborah L
DL
Birx
U.S. Military HIV Research Program, Henry M. Jackson Foundation, Silver Spring, Maryland, United States of America.
Silvia
S
Ratto-Kim
U.S. Military HIV Research Program, Henry M. Jackson Foundation, Silver Spring, Maryland, United States of America.
Merlin L
ML
Robb
International Vaccine Institute, Seoul, Republic of Korea; U.S. Military HIV Research Program, Water Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Jerome H
JH
Kim
U.S. Military HIV Research Program, Water Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Nelson L
NL
Michael
Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
Haitao
H
Hu
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans; D002177:Candidiasis / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D016133:Polymerase Chain Reaction; D059467:Transcriptome