Streptococcal Histone Induces Murine Macrophages To Produce Interleukin-1 and Tumor Necrosis Factor Alpha

Abstract

The histone-like protein (HlpA) is highly conserved among streptococci. After lysis of streptococci in infected tissues, HlpA can enter the bloodstream and bind to proteoglycans in the glomerular capillaries of kidneys, where it can react with antibodies or stimulate host cell receptors. Deposits of streptococcal antigens in tissues have been associated with localized acute inflammation. In this study, we measured the ability of purified HlpA (5 to 100 g/ml), from Streptococcus mitis, to induce the production of proinflammatory cytokines by cultured, murine peritoneal macrophages. The release of tumor necrosis factor alpha (TNF-␣) and interleukin-1 (IL-1) was time and concentration dependent and was not diminished by the presence of polymyxin B. Exposure of macrophages to a mixture of HlpA and lipoteichoic acid resulted in a synergistic response in the production of both TNF-␣ and IL-1. Stimulation with a mixture of HlpA and heparin resulted in reduced cytokine production (50% less IL-1 and 76% less TNF-␣) compared to that by cells incubated with HlpA alone. The inclusion of antibodies specific to HlpA in macrophage cultures during stimulation with HlpA did not affect the quantity of TNF-␣ or IL-1 produced. These observations suggest that streptococcal histone may contribute to tissue injury at infection sites by promoting monocytes/macrophages to synthesize and release cytokines that initiate and exacerbate inflammation. Streptococcus pyogenes, which can infect tissues in enormous numbers, may release sufficient amounts of HlpA to reach the kidneys and cause acute poststreptococcal glomerulonephritis.

B‐cell activation by T‐cell‐independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms

“…The macrophage is another member of the innate immune system that can be stimulated by microbial antigens (257)(258)(259) and CpG ODN (260)(261)(262)(263)(264) to secrete IL-1, IL-6, IL-12 and granulocyte-macrophage colony-stimulatory factor to provide B cells that are activated by multivalent mIg cross-linking, with second signals. Mast cells can be stimulated by microbial products to secrete IL-6, and by IL-12 to produce IFN-g (265)(266)(267)(268).…”

Aberrant Community Architecture and Attenuated Persistence of Uropathogenic Escherichia coli in the Absence of Individual IHF Subunits

“…The DNABII family of proteins is also observed in the extrabacterial milieu [23] – [25] . The extrabacterial accumulation of the Streptococcus DNABII family member, HlpA, elicits a proinflammatory immune response in macrophages [26] that may contribute to tissue damage associated with infection.…”

Proteomic Investigation of the Response of Enterococcus faecalis V583 when Cultivated in Urine

“…Interestingly, in streptococci, HlpA, which is predicted to be cytoplasmic, has been detected on the cell surface, where it forms complexes with lipoteichoid acid (LTA) and mediates bacterial adherence by also interacting with heparan sulfate proteoglycans of host cells [ 58 , 59 ]. Binding of HlpA-LTA complexes to host cells is known to stimulate production of pro-inflammatory cytokines in cultured murine macrophages, suggesting a role of HlpA in promoting tissue damage at infection sites [ 60 ]. To our knowledge, regulation of EF1550 in response to a urine environment has not been reported before.…”