Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria-Reference-Cited by-同舟云学术

Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria

Published:2023-01-25 Issue:680 Volume:15 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Ty Maureen¹^ORCID,Sun Shenghuan²,Callaway Perri C.³^ORCID,Rek John⁴^ORCID,Press Kathleen D.¹^ORCID,van der Ploeg Kattria¹^ORCID,Nideffer Jason¹,Hu Zicheng²^ORCID,Klemm Sandy⁵,Greenleaf William⁵^ORCID,Donato Michele⁶^ORCID,Tukwasibwe Stephen⁴^ORCID,Arinaitwe Emmanuel⁴,Nankya Felistas⁴,Musinguzi Kenneth⁴,Andrew Dean⁷^ORCID,de la Parte Lauren¹,Mori Diego Martinez¹,Lewis Savannah N.¹^ORCID,Takahashi Saki³^ORCID,Rodriguez-Barraquer Isabel³^ORCID,Greenhouse Bryan³^ORCID,Blish Catherine¹⁸^ORCID,Utz PJ¹^ORCID,Khatri Purvesh⁶^ORCID,Dorsey Grant³^ORCID,Kamya Moses⁴⁹,Boyle Michelle⁷^ORCID,Feeney Margaret³¹⁰^ORCID,Ssewanyana Isaac⁴,Jagannathan Prasanna¹¹¹^ORCID

Affiliation:

1. Department of Medicine, Stanford University, Stanford, CA, USA.

2. Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.

3. Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

4. Infectious Diseases Research Collaboration, Kampala, Uganda.

5. Department of Genetics, Stanford University, Stanford, CA, USA.

6. Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.

7. Queensland Institute for Medical Research, Queensland, Australia.

8. Chan Zuckerberg Biohub, San Francisco, CA, USA.

9. Department of Medicine, Makerere University, Kampala, Uganda.

10. Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.

11. Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.

Abstract

Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56 neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56 dim NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56 neg NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56 dim NK cells. Higher frequencies of CD56 neg NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to Plasmodium falciparum is required to maintain this modified, adaptive-like NK cell subset.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Link

https://www.science.org/doi/pdf/10.1126/scitranslmed.add9012

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