Researchers from the University of Miami's Miller School of Medicine have published the results of a new study that could help develop better treatment strategies bacterial gastrointestinal infections, according to a news release.
The study focuses on the cellular signaling pathways in the body's immune system response.
The results were published in a recent issue of the Journal of Experimental Medicine.
"Our results demonstrate a previously unknown role of the pathway that recognizes these pathogens and stimulates the immune response," said Masayuki Fukata, PhD, assistant professor of medicine in the division of gastroenterology, and the study's senior author, in the release. "Our results provide an important way to activate the body's innate immune response without causing systemic toxicity. We envision that targeting this pathway can be a new approach to treating patients within a window of infection."
The study's abstract reads as the following:
"Toll-like receptor 4 (TLR4), which signals through the adapter molecules myeloid differentiation factor 88 (MyD88) and toll/interleukin 1 receptor domain-containing adapter inducing IFN-β (TRIF), is required for protection against Gram-negative bacteria. TRIF is known to be important in TLR3-mediated antiviral signaling, but the role of TRIF signaling against Gram-negative enteropathogens is currently unknown. We show that TRIF signaling is indispensable for establishing innate protective immunity against Gram-negative Yersinia enterocolitica. Infection of wild-type mice rapidly induced both IFN-β and IFN-γ in the mesenteric lymph nodes. In contrast, TRIF-deficient mice were defective in these IFN responses and showed impaired phagocytosis in regional macrophages, resulting in greater bacterial dissemination and mortality. TRIF signaling may be universally important for protection against Gram-negative pathogens, as TRIF-deficient macrophages were also impaired in killing both Salmonella and Escherichia coli in vitro. The mechanism of TRIF-mediated protective immunity appears to be orchestrated by macrophage-induced IFN-β and NK cell production of IFN-γ. Sequential induction of IFN-β and IFN-γ leads to amplification of macrophage bactericidal activity sufficient to eliminate the invading pathogens at the intestinal interface. Our results demonstrate a previously unknown role of TRIF in host resistance to Gram-negative enteropathogens, which may lead to effective strategies for combating enteric infections."
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