Streptococcal modulation of cellular invasion via TGF-β1 signaling

Beinan Wang, Shaoying Li, Peter Southern, Patrick P. Cleary

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Group A Streptococcus (GAS) and other bacterial pathogens are known to interact with integrins as an initial step in a complex pathway of bacterial ingestion by host cells. Efficient GAS invasion depends on the interaction of bound fibronectin (Fn) with integrins and activation of integrin signaling. TGF-β1 regulates expression of integrins, Fn, and other extracellular matrix proteins, and positively controls the integrin signaling pathway. Therefore, we postulated that TGF-β1 levels could influence streptococcal invasion of mammalian cells. Pretreatment of HEp-2 cells with TGF-β1 increased their capacity to ingest GAS when the bacteria expressed fibronectin-binding proteins (M1 or PrtF1). Western blots revealed significant induction of α5 integrin and Fn expression by HEp-2 cells in response to TGF-β1. Increased ingestion of streptococci by these cells was blocked by a specific inhibitor of the TGF-β1 receptor I and antibodies directed against α5 integrin and Fn, indicating that increased invasion depends on TGF-β1 up-regulation of both the α5 integrin and Fn. The capacity of TGF-β1 to up-regulate integrin expression and intracellular invasion by GAS was reproduced in primary human tonsil fibroblasts, which could be a source of TGF-β1 in chronically infected tonsils. The relationship between TGF-β1 and GAS invasion was strengthened by the observation that TGF-β1 production was stimulated in GAS-infected primary human tonsil fibroblasts. These findings suggest a mechanism by which GAS induce a cascade of changes in mammalian tissue leading to elevated expression of the α5β1 receptor, enhanced invasion, and increased opportunity for survival and persistence in their human host.

Original languageEnglish (US)
Pages (from-to)2380-2385
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 14 2006


  • Fibronectin
  • Fibronectin binding protein
  • Integrin
  • Tonsils


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