Group 1 CD1-restricted T cells contribute to control of systemic Staphylococcus aureus infection.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
04 2020
Historique:
received: 25 09 2019
accepted: 28 02 2020
entrez: 29 4 2020
pubmed: 29 4 2020
medline: 28 7 2020
Statut: epublish

Résumé

Staphylococcus aureus (SA) is the causative agent of both skin/soft tissue infections as well as invasive bloodstream infections. Though vaccines have been developed to target both humoral and T cell-mediated immune responses against SA, they have largely failed due to lack of protective efficacy. Group 1 CD1-restricted T cells recognize lipid rather than peptide antigens. Previously found to recognize lipids derived from cell wall of Mycobacterium tuberculosis (Mtb), these cells were associated with protection against Mtb infection in humans. Using a transgenic mouse model expressing human group 1 CD1 molecules (hCD1Tg), we demonstrate that group 1 CD1-restricted T cells can recognize SA-derived lipids in both immunization and infection settings. Systemic infection of hCD1Tg mice showed that SA-specific group 1 CD1-restricted T cell response peaked at 10 days post-infection, and hCD1Tg mice displayed significantly decreased kidney pathology at this time point compared with WT control mice. Immunodominant SA lipid antigens recognized by group 1 CD1-restricted T cells were comprised mainly of cardiolipin and phosphatidyl glycerol, with little contribution from lysyl-phosphatidyl glycerol which is a unique bacterial lipid not present in mammals. Group 1 CD1-restricted T cell lines specific for SA lipids also conferred protection against SA infection in the kidney after adoptive transfer. They were further able to effectively control SA replication in vitro through direct antigen presentation by group 1 CD1-expressing BMDCs. Together, our data demonstrate a previously unknown role for group 1 CD1-restricted SA lipid-specific T cells in the control of systemic MRSA infection.

Identifiants

pubmed: 32343740
doi: 10.1371/journal.ppat.1008443
pii: PPATHOGENS-D-19-01794
pmc: PMC7188215
doi:

Substances chimiques

Antigens, CD1 0
Lipids 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008443

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI120994
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008061
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI057460
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007476
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Lavanya Visvabharathy (L)

Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

Samantha Genardi (S)

Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

Liang Cao (L)

Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

Ying He (Y)

Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

Francis Alonzo (F)

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University, Maywood, United States of America.

Evgeny Berdyshev (E)

Department of Medicine, National Jewish Health, Denver, United States of America.

Chyung-Ru Wang (CR)

Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

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