Natural killer cell phenotype is altered in HIV-exposed seronegative women

Nancy Zhao; Elena Vendrame; Anne-Maud Ferreira; Christof Seiler; Thanmayi Ranganath; Michel Alary; Annie-Claude Labbé; Fernand Guédou; Johanne Poudrier; Susan P Holmes; Michel Roger; Catherine A Blish

doi:10.1371/journal.pone.0238347

Natural killer cell phenotype is altered in HIV-exposed seronegative women

Nancy Zhao, Elena Vendrame, Anne-Maud Ferreira, Christof Seiler, Thanmayi Ranganath, Michel Alary, Annie-Claude Labbé, Fernand Guédou, Johanne Poudrier, Susan P Holmes, Michel Roger^*, Catherine A Blish^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls.
We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4+ T cells, we observed that NKp30+ and Siglec-7+ cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with larger
cohorts are warranted to confirm these findings.

Original language	English
Article number	e0238347
Pages (from-to)	1-17
Number of pages	17
Journal	PLOS ONE
Volume	15
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0238347
Publication status	Published - 1 Sept 2020

Keywords

ACQUISITION
ACTIVATION
ANTIBODY
CYTOTOXICITY RESPONSES
HLA-B
INFECTION
KIR3DL1
MEDIATED CYTOTOXICITY
NK CELLS
PROGRESSION

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Cite this

@article{947df7271bfa432b8d1f5ffcd30f8657,

title = "Natural killer cell phenotype is altered in HIV-exposed seronegative women",

abstract = "Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls.We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4+ T cells, we observed that NKp30+ and Siglec-7+ cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with largercohorts are warranted to confirm these findings.",

keywords = "ACQUISITION, ACTIVATION, ANTIBODY, CYTOTOXICITY RESPONSES, HLA-B, INFECTION, KIR3DL1, MEDIATED CYTOTOXICITY, NK CELLS, PROGRESSION",

author = "Nancy Zhao and Elena Vendrame and Anne-Maud Ferreira and Christof Seiler and Thanmayi Ranganath and Michel Alary and Annie-Claude Labb{\'e} and Fernand Gu{\'e}dou and Johanne Poudrier and Holmes, {Susan P} and Michel Roger and Blish, {Catherine A}",

note = "Funding Information: This work was supported by: NIH Ruth L. Kirschstein Institutional National Research Service Award T32 AI007502 and TL1 TR001084 (EV), NIH/NIAID K08 AI138640 (EV), ITI/Bill & Melinda Gates Foundation Pilot Grant (CAB), NIH/NIAID DP2 AI112193 (CAB), NIH/NIDA Avant Garde Award for HIV Research DP1 DA046089 (CAB), Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases (CAB), Grant # PJT-148529 from the Canadian Institutes of Health Research and by the R{\'e}seau SIDA from the Fonds de Recherche du Qu{\'e}bec en Sant{\'e} (MR). NQZ was supported by a National Science Scholarship from the Agency of Science, Technology and Research (A*STAR) Singapore. CAB is an investigator of the Chan Zuckerberg Biohub. We are grateful to the Beninese study participants. We are indebted to N. Geraldo, A. Gabin, C. Assogba and C. Agossa-Gbenafa for their clinical expertise, to M. Massinga-Loembe, G. Ahotin, L.Djossou and E. Goma for their technical assistance and to G. Batona and other field workers who helped with recruitment of commercial sex workers. We also thank the Human Immune Monitoring Core (HIMC) at Stanford University for use of their Helios machine. Publisher Copyright: {\textcopyright} 2020 Zhao 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.",

year = "2020",

month = sep,

day = "1",

doi = "10.1371/journal.pone.0238347",

language = "English",

volume = "15",

pages = "1--17",

journal = "PLOS ONE",

issn = "1932-6203",

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TY - JOUR

T1 - Natural killer cell phenotype is altered in HIV-exposed seronegative women

AU - Zhao, Nancy

AU - Vendrame, Elena

AU - Ferreira, Anne-Maud

AU - Seiler, Christof

AU - Ranganath, Thanmayi

AU - Alary, Michel

AU - Labbé, Annie-Claude

AU - Guédou, Fernand

AU - Poudrier, Johanne

AU - Holmes, Susan P

AU - Roger, Michel

AU - Blish, Catherine A

N1 - Funding Information: This work was supported by: NIH Ruth L. Kirschstein Institutional National Research Service Award T32 AI007502 and TL1 TR001084 (EV), NIH/NIAID K08 AI138640 (EV), ITI/Bill & Melinda Gates Foundation Pilot Grant (CAB), NIH/NIAID DP2 AI112193 (CAB), NIH/NIDA Avant Garde Award for HIV Research DP1 DA046089 (CAB), Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases (CAB), Grant # PJT-148529 from the Canadian Institutes of Health Research and by the Réseau SIDA from the Fonds de Recherche du Québec en Santé (MR). NQZ was supported by a National Science Scholarship from the Agency of Science, Technology and Research (A*STAR) Singapore. CAB is an investigator of the Chan Zuckerberg Biohub. We are grateful to the Beninese study participants. We are indebted to N. Geraldo, A. Gabin, C. Assogba and C. Agossa-Gbenafa for their clinical expertise, to M. Massinga-Loembe, G. Ahotin, L.Djossou and E. Goma for their technical assistance and to G. Batona and other field workers who helped with recruitment of commercial sex workers. We also thank the Human Immune Monitoring Core (HIMC) at Stanford University for use of their Helios machine. Publisher Copyright: © 2020 Zhao 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.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls.We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4+ T cells, we observed that NKp30+ and Siglec-7+ cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with largercohorts are warranted to confirm these findings.

AB - Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls.We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4+ T cells, we observed that NKp30+ and Siglec-7+ cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with largercohorts are warranted to confirm these findings.

KW - ACQUISITION

KW - ACTIVATION

KW - ANTIBODY

KW - CYTOTOXICITY RESPONSES

KW - HLA-B

KW - INFECTION

KW - KIR3DL1

KW - MEDIATED CYTOTOXICITY

KW - NK CELLS

KW - PROGRESSION

U2 - 10.1371/journal.pone.0238347

DO - 10.1371/journal.pone.0238347

M3 - Article

C2 - 32870938

SN - 1932-6203

VL - 15

SP - 1

EP - 17

JO - PLOS ONE

JF - PLOS ONE

IS - 9

M1 - e0238347

ER -