Lymph node CXCR5+ NK cells associate with control of chronic SHIV infection.

Autor: Rahman SA; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Microbiology and Immunology and., Billingsley JM; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA., Sharma AA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Styles TM; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA., Govindaraj S; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Shanmugasundaram U; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA., Babu H; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Riberio SP; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Ali SA; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, Louisiana, USA., Tharp GK; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA., Ibegbu C; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA., Waggoner SN; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Johnson RP; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Microbiology and Immunology and.; Infectious Disease Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Sekaly RP; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Villinger F; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, Louisiana, USA., Bosinger SE; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Amara RR; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Microbiology and Immunology and., Velu V; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2022 Apr 22; Vol. 7 (8). Date of Electronic Publication: 2022 Apr 22.
DOI: 10.1172/jci.insight.155601
Abstrakt: The persistence of virally infected cells as reservoirs despite effective antiretroviral therapy is a major barrier to an HIV/SIV cure. These reservoirs are predominately contained within cells present in the B cell follicles (BCFs) of secondary lymphoid tissues, a site that is characteristically difficult for most cytolytic antiviral effector cells to penetrate. Here, we identified a population of NK cells in macaque lymph nodes that expressed BCF-homing receptor CXCR5 and accumulated within BCFs during chronic SHIV infection. These CXCR5+ follicular NK cells exhibited an activated phenotype coupled with heightened effector functions and a unique transcriptome characterized by elevated expression of cytolytic mediators (e.g., perforin and granzymes, LAMP-1). CXCR5+ NK cells exhibited high expression of FcγRIIa and FcγRIIIa, suggesting a potential for elevated antibody-dependent effector functionality. Consistently, accumulation of CXCR5+ NK cells showed a strong inverse association with plasma viral load and the frequency of germinal center follicular Th cells that comprise a significant fraction of the viral reservoir. Moreover, CXCR5+ NK cells showed increased expression of transcripts associated with IL-12 and IL-15 signaling compared with the CXCR5- subset. Indeed, in vitro treatment with IL-12 and IL-15 enhanced the proliferation of CXCR5+ granzyme B+ NK cells. Our findings suggest that follicular homing NK cells might be important in immune control of chronic SHIV infection, and this may have important implications for HIV cure strategies.
Databáze: MEDLINE