Natural killer-like B cells are a distinct but infrequent innate immune cell subset modulated by SIV infection of rhesus macaques.

Autor: Manickam C; Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University, Durham, North Carolina, United States of America.; Department of Surgery, Duke University, Durham, North Carolina, United States of America., Upadhyay AA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.; Division of Microbiology and Immunology, Emory National Primate Research Center, Atlanta, Georgia, United States of America., Woolley G; Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University, Durham, North Carolina, United States of America.; Department of Surgery, Duke University, Durham, North Carolina, United States of America., Kroll KW; Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University, Durham, North Carolina, United States of America.; Department of Surgery, Duke University, Durham, North Carolina, United States of America., Terry K; Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University, Durham, North Carolina, United States of America.; Department of Surgery, Duke University, Durham, North Carolina, United States of America., Broedlow CA; Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America., Klatt NR; Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America., Bosinger SE; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.; Division of Microbiology and Immunology, Emory National Primate Research Center, Atlanta, Georgia, United States of America., Reeves RK; Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University, Durham, North Carolina, United States of America.; Department of Surgery, Duke University, Durham, North Carolina, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 May 13; Vol. 20 (5), pp. e1012223. Date of Electronic Publication: 2024 May 13 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012223
Abstrakt: Natural killer-like B (NKB) cells are unique innate immune cells expressing both natural killer (NK) and B cell receptors. As first responders to infection, they secrete IL-18 to induce a critical cascade of innate and adaptive immune cell infiltration and activation. However, limited research exists on the role of NKB cells in homeostasis and infection, largely due to incomplete and erroneous evaluations. To fill this knowledge gap, we investigated the expression of signaling and trafficking proteins, and the in situ localization and transcriptome of naïve NKB cells compared to conventionally-defined NK and B cells, as well as modulations of these cells in SIV infection. Intracellular signaling proteins and trafficking markers were expressed differentially on naïve NKB cells, with high expression of CD62L and Syk, and low expression of CD69, α4β7, FcRg, Zap70, and CD3z, findings which were more similar to B cells than NK cells. CD20+NKG2a/c+ NKB cells were identified in spleen, mesenteric lymph nodes (MLN), colon, jejunum, and liver of naïve rhesus macaques (RM) via tissue imaging, with NKB cell counts concentrated in spleen and MLN. For the first time, single cell RNA sequencing (scRNAseq), including B cell receptor (BCR) sequencing, of sorted NKB cells confirmed that NKB cells are unique. Transcriptomic analysis of naïve splenic NKB cells by scRNAseq showed that NKB cells undergo somatic hypermutation and express Ig receptors, similar to B cells. While only 15% of sorted NKB cells showed transcript expression of both KLRC1 (NKG2A) and MS4A1 (CD20) genes, only 5% of cells expressed KLRC1, MS4A1, and IgH/IgL transcripts. We observed expanded NKB frequencies in RM gut and buccal mucosa as early as 14 and 35 days post-SIV infection, respectively. Further, mucosal and peripheral NKB cells were associated with colorectal cytokine milieu and oral microbiome changes, respectively. Our studies indicate that NKB cells gated on CD3-CD14-CD20+NKG2A/C+ cells were inclusive of transcriptomically conventional B and NK cells in addition to true NKB cells, confounding accurate phenotyping and frequency recordings that could only be resolved using genomic techniques. Although NKB cells were clearly elevated during SIV infection and associated with inflammatory changes during infection, further interrogation is necessary to acurately identify the true phenotype and significance of NKB cells in infection and inflammation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Manickam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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