Systemic Activation of TLR3-Dependent TRIF Signaling Confers Host Defense against Gram-Negative Bacteria in the Intestine.

Recognition of Gram-negative bacteria by toll-like receptor (TLR)4 induces MyD88 and TRIF mediated responses. We have shown that TRIF-dependent responses play an important role in intestinal defense against Gram-negative enteropathogens. In the current study, we examined underlying mechanisms of how systemic TRIF activation enhances intestinal immune defense against Gram-negative bacteria.

TIR Domain-Containing Adapter-Inducing Beta Interferon (TRIF) Mediates Immunological Memory against Bacterial Pathogens.

Induction of adaptive immunity leads to the establishment of immunological memory; however, how innate immunity regulates memory T cell function remains obscure. Here we show a previously undefined mechanism in which innate and adaptive immunity are linked by TIR domain-containing adapter-inducing beta interferon (TRIF) during establishment and reactivation of memory T cells against Gram-negative enteropathogens. Absence of TRIF in macrophages (Mϕs) but not dendritic cells led to a predominant generation of CD4(+) central memory T cells that express IL-17 during enteric bacterial infection in mice.

Human intestinal epithelial cells express interleukin-10 through Toll-like receptor 4-mediated epithelial-macrophage crosstalk.

In the intestine, interaction between epithelial cells and macrophages (MΦs) create a unique immunoregulatory microenvironment necessary to maintain local immune and tissue homeostasis. Human intestinal epithelial cells (IECs) have been shown to express interleukin (IL)-10, which keeps epithelial integrity. We have demonstrated that bacterial signaling through Toll-like receptor (TLR) 4 induces 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) synthesis in intestinal MΦs by cyclooxygenase (Cox)-2 expression.

TIR-domain-containing adapter-inducing interferon-β (TRIF) regulates Th17-mediated intestinal immunopathology in colitis.

Gastrointestinal mucosa reserves abundant Th17 cells where host response to commensal bacteria maintains Th17-cell generation. Although functional heterogeneity and dynamic plasticity of Th17 cells appear to be involved in chronic inflammatory disorders, how their plasticity is regulated in intestinal mucosa is unknown. Here we show that innate TRIF signaling regulates intestinal Th17-cell generation and plasticity during colitis.

Expanding global distribution of rotavirus serotype G9: detection in Libya, Kenya, and Cuba.

Serotype G9 may be the fifth most common human rotavirus serotype, after serotypes G1 to G4. In three cross-sectional studies of childhood diarrhea, we have detected serotype G9 rotaviruses for the first time in Libya, Kenya, and Cuba. Serotype G9 constituted 27% of all rotaviruses identified, emphasizing the reemergence of serotype G9 and suggesting that future human rotavirus vaccines will need to protect against disease caused by this serotype.