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. TRIF-dependent type I interferon (IFN) signaling in T cells was essential to Th1 lineage differentiation and reactivation of memory T cells. TRIF activated memory T cells to facilitate local neutrophil influx and enhance bacterial elimination. These results highlight the importance of TRIF as a mediator of the innate and adaptive immune interactions in achieving the protective properties of memory immunity against Gram-negative bacteria and suggest TRIF as a potential therapeutic target.
Division of Gastroenterology, Department of Medicine, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Saravana
S
Kanagavelu
Division of Gastroenterology, Department of Medicine, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Claudia
C
Flores
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
J M
JM
Termini
Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
Laura
L
Romero
Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
Reldy
R
Riveron
Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jose
J
Ruiz
Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, California, USA Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Moshe
M
Arditi
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Kurt
K
Schesser
Division of Gastroenterology, Department of Medicine, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA Masayuki.fukata@cshs.org.
Masayuki
M
Fukata
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D015009:Yersinia Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000235:genetics / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; D007371:Interferon-gamma; D020381:Interleukin-17; C476286:Ticam1 protein, mouse