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

Maureen Ty; Shenghuan Sun; Perri C Callaway; John Rek; Kathleen D Press; Kattria van der Ploeg; Jason Nideffer; Zicheng Hu; Sandy Klemm; William Greenleaf; Michele Donato; Stephen Tukwasibwe; Emmanuel Arinaitwe; Felistas Nankya; Kenneth Musinguzi; Dean Andrew; Lauren de la Parte; Diego Martinez Mori; Savannah N Lewis; Saki Takahashi; Isabel Rodriguez-Barraquer; Bryan Greenhouse; Catherine Blish; P J Utz; Purvesh Khatri; Grant Dorsey; Moses Kamya; Michelle Boyle; Margaret Feeney; Isaac Ssewanyana; Prasanna Jagannathan

doi:10.1126/scitranslmed.add9012

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

Sci Transl Med. 2023 Jan 25;15(680):eadd9012. doi: 10.1126/scitranslmed.add9012. Epub 2023 Jan 25.

Authors

Maureen Ty¹, Shenghuan Sun², Perri C Callaway³, John Rek⁴, Kathleen D Press¹, Kattria van der Ploeg¹, Jason Nideffer¹, Zicheng Hu², Sandy Klemm⁵, William Greenleaf⁵, Michele Donato⁶, Stephen Tukwasibwe⁴, Emmanuel Arinaitwe⁴, Felistas Nankya⁴, Kenneth Musinguzi⁴, Dean Andrew⁷, Lauren de la Parte¹, Diego Martinez Mori¹, Savannah N Lewis¹, Saki Takahashi³, Isabel Rodriguez-Barraquer³, Bryan Greenhouse³, Catherine Blish^{1

8}, P J Utz¹, Purvesh Khatri⁶, Grant Dorsey³, Moses Kamya^{4

9}, Michelle Boyle⁷, Margaret Feeney^{3

10}, Isaac Ssewanyana⁴, Prasanna Jagannathan^{1

11}

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD56 Antigen / metabolism
Child
Humans
Killer Cells, Natural*
Malaria*
Plasmodium falciparum
Receptors, Fc

Substances

CD56 Antigen
Receptors, Fc

Abstract

Publication types

MeSH terms

Substances

Grants and funding