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.

Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections

“…aureus infection can form abscesses and persist in different organs. The kidneys are frequently the most affected ones, displaying high bacterial burdens [ 69 ]. In the present study, the main lesions were identified in the liver and kidneys as foci of neutrophil infiltration with abscess formation.…”

From Host Defense to Metabolic Signatures: Unveiling the Role of γδ T Cells in Bacterial Infections

“…Some mice in this study were also found to have a biphasic wave of IL-17 production, with one peak at 3 h and the second at 72 h post-infection, with Vγ4+ γδ T cells at 72 h being primed for later infection and IL-1β independent IL-17 production [18], suggesting a memory function for γδ T cells during acute peritonitis as well. In the kidney, chronic systemic S. aureus infection induced the expansion of a population of kidney-resident γδ T cells that constitutively express CD69 and provide protection against S. aureus [15]. Thus, in mice, S. aureus infection seems to expand both resident and memory γδ T cells.…”

“…Vγ4+ cells increase in number through development [12]. Vγ4+ γδ T cells typically make IFNγ cytokine, while Vγ6+ γδ T cells typically make IL-17 and IL-22 [15]. Thymic signals regulate these cells' subsequent effector function and critical role during early infection stages [16].…”

T cells in health and disease

“… 970 , 971 Systemic S. aureus infection led to accumulation of IL-17A + γδ T cells in the kidney for effective infection control. 972 In the infected intestinal tract, Vγ7 + γδ T cells directly kill infected cells by secreting antimicrobial peptides and cytotoxic molecules. 973 In Mtb infected lung tissue, Vγ4 + γδ T cells secrete CXCL2 and TNF to promote neutrophil recruitment and Vγ4 + and Vγ6 + Tγδ17 cells contribute to granuloma formation.…”