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

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 Ca(2+) fluxes to activate calpains and caspase-3. Although human airway epithelial cells, vascular endothelial cells, THP-1 and Jurkat T cells 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+)/calpain signaling contribute to T cell activation and excessive inflammation in the setting of acute pneumonia.

SUBMITTER: Ahn DS

PROVIDER: S-EPMC4199935 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Ahn D S DS Parker D D Planet P J PJ Nieto P A PA Bueno S M SM Prince A A

Mucosal immunology 20140416 6

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 ...[more]

PMID: 24736233

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

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

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