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Kidney-resident innate-like memory γδ T cells control chronic Staphylococcus aureus infection of mice.

ABSTRACT: γδ T cells are involved in the control of Staphylococcus aureus infection, but their importance in protection compared to other T cells is unclear. We used a mouse model of systemic S. aureus infection associated with high bacterial load and persistence in the kidney. Infection caused fulminant accumulation of γδ T cells in the kidney. Renal γδ T cells acquired tissue residency and were maintained in high numbers during chronic infection. At day 7, up to 50% of renal γδ T cells produced IL-17A in situ and a large fraction of renal γδ T cells remained IL-17A+ during chronic infection. Controlled depletion revealed that γδ T cells restricted renal S. aureus replication in the acute infection and provided protection during chronic renal infection and upon reinfection. Our results demonstrate that kidney-resident γδ T cells are nonredundant in limiting local S. aureus growth during chronic infection and provide enhanced protection against reinfection.

SUBMITTER: Bertram T

PROVIDER: S-EPMC9910431 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Kidney-resident innate-like memory γδ T cells control chronic Staphylococcus aureus infection of mice.

Bertram Tabea T Reimers Daniel D Lory Niels C NC Schmidt Constantin C Schmid Joanna J C Heinig Lisa L Bradtke Peter P Rattay Guido G Zielinski Stephanie S Hellmig Malte M Bartsch Patricia P Rohde Holger H Nuñez Sarah S Rosemblatt Mariana V MV Bono Maria Rosa MR Gagliani Nicola N Sandrock Inga I Panzer Ulf U Krebs Christian F CF Meyer-Schwesinger Catherine C Prinz Immo I Mittrücker Hans-Willi HW

Proceedings of the National Academy of Sciences of the United States of America 20221227 1

γδ T cells are involved in the control of Staphylococcus aureus infection, but their importance in protection compared to other T cells is unclear. We used a mouse model of systemic S. aureus infection associated with high bacterial load and persistence in the kidney. Infection caused fulminant accumulation of γδ T cells in the kidney. Renal γδ T cells acquired tissue residency and were maintained in high numbers during chronic infection. At day 7, up to 50% of renal γδ T cells pro ...[more]

PMID: 36574651

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Project description:IntroductionThe mechanisms underlying innate immune memory (trained immunity) comprise epigenetic reprogramming of transcriptional pathways associated with alterations of intracellular metabolism. While the mechanisms of innate immune memory carried out by immune cells are well characterized, such processes in non-immune cells, are poorly understood. The opportunistic pathogen, Staphylococcus aureus, is responsible for a multitude of human diseases, including pneumonia, endocarditis and osteomyelitis, as well as animal infections, including chronic cattle mastitis that are extremely difficult to treat. An induction of innate immune memory may be considered as a therapeutic alternative to fight S. aureus infection.MethodsIn the current work, we demonstrated the development of innate immune memory in non-immune cells during S. aureus infection employing a combination of techniques including Enzyme-linked immunosorbent assay (ELISA), microscopic analysis, and cytometry.ResultsWe observed that training of human osteoblast-like MG-63 cells and lung epithelial A549 cells with β-glucan increased IL-6 and IL-8 production upon a stimulation with S. aureus, concomitant with histones modifications. IL-6 and IL-8 production was positively correlated with an acetylation of histone 3 at lysine 27 (H3K27), thus suggesting epigenetic reprogramming in these cells. An addition of the ROS scavenger N-Acetylcysteine, NAC, prior to β-glucan pretreatment followed by an exposure to S. aureus, resulted in decreased IL-6 and IL-8 production, thereby supporting the involvement of ROS in the induction of innate immune memory. Exposure of cells to Lactococcus lactis resulted in increased IL-6 and IL-8 production by MG-63 and A549 cells upon a stimulation with S. aureus that was correlated with H3K27 acetylation, suggesting the ability of this beneficial bacterium to induce innate immune memory.DiscussionThis work improves our understanding of innate immune memory in non-immune cells in the context of S. aureus infection. In addition to known inducers, probiotics may represent good candidates for the induction of innate immune memory. Our findings may help the development of alternative therapeutic approaches for the prevention of S. aureus infection.

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Kidney-resident innate-like memory γδ T cells control chronic Staphylococcus aureus infection of mice.

Publications

Kidney-resident innate-like memory γδ T cells control chronic <i>Staphylococcus aureus</i> infection of mice.

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