Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to MRSA pneumonia

Ahn, DS; Parker D.; Planet, PJ; Nieto, PA; Bueno, SM; Prince, A

Abstract

Staphylococcus aureus is a major cause of severe pneumonia. Multiple mechanisms of proinflammatory signaling are activated to recruit immune cells into the airway in response to S. aureus. We found that interleukin-16 (IL-16), a T cell cytokine that binds CD4, is potently activated by S. aureus, specifically by protein A (SpA), and to a much greater extent than by Gram-negative pathogens or lipopolysaccharide. IL-16 production involved multiple signals including ligation of tumor necrosis factor receptor (TNFR) family members or epidermal growth factor receptor, both receptors for SpA and generation of Ca2+ fluxes to activate calpains and caspase-3. Although human airway epithelial cells, vascular endothelial cells, THP-1 and Jurkat Tcells released IL-16 in response to S. aureus in vitro, in a murine model of pneumonia, CD4+ cells were the major source of IL-16 suggesting the involvement of an autocrine signaling pathway. The production of IL-16 contributed to lung damage as neutralization of IL-16 enhanced S. aureus clearance and resulted in diminished lung pathology in S. aureus pneumonia. Our results suggest that the ability of S. aureus to activate TNFR1 and Ca-2 broken vertical bar /calpain signaling contribute to T cell activation and excessive inflammation in the setting of acute pneumonia.

Más información

Título según WOS: Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to MRSA pneumonia
Título según SCOPUS: Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to MRSA pneumonia
Título de la Revista: MUCOSAL IMMUNOLOGY
Volumen: 7
Número: 6
Editorial: Elsevier Science Inc.
Fecha de publicación: 2014
Página de inicio: 1366
Página final: 1374
Idioma: English
DOI:

10.1038/mi.2014.24

Notas: ISI, SCOPUS