The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.
Bottom Line: The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response.So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host.The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype.
Affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.Show MeSH
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Mentions: We next investigated the relevance of the adaptive immune response for controlling S. aureus during the persistent phase of the infection using B and T cells-deficient RAG2−/− mice. The results in Fig 5A show that RAG2−/− mice exhibited a higher, more sustained bacterial burden in the kidneys during the persistent phase than immunocompentent C57BL/6 animals. Similarly, RAG2/IL-2Rγ−/− mice, which are devoid of B, T and natural killer (NK) cells, were significantly less capable of containing S. aureus during the persistent phase of infection than C57BL/6 mice (Fig S4 of Supporting information). These observations demonstrate that B and/or T cells are responsible for the superior restriction of S. aureus proliferation observed in C57BL/6 mice. Nevertheless, RAG2−/− and RAG2/IL-2Rγ−/− mice were also able to exert certain levels of control over S. aureus proliferation in the kidneys during the persistent phase that was mediated by innate immune mechanisms since depletion of neutrophils or macrophages resulted in enhanced bacterial multiplication in this organ (Fig S5 of Supporting information).
Affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.