Abstract
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 (Mπs) 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. TRIFdependent 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4404-4415 |
| Number of pages | 12 |
| Journal | Infection and Immunity |
| Volume | 83 |
| Issue number | 11 |
| DOIs | |
| State | Published - 2015 |
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ASJC Scopus subject areas
- Immunology
- Microbiology
- Parasitology
- Infectious Diseases
Cite this
TIR domain-containing adapter-inducing beta interferon (TRIF) mediates immunological memory against bacterial pathogens. / Kanagavelu, Saravana; Flores, Claudia; M. Termini, J.; Romero, Laura; Riveron, Reldy; Ruiz, Jose; Arditi, Moshe; Schesser, Kurt; Fukata, Masayuki.
In: Infection and Immunity, Vol. 83, No. 11, 2015, p. 4404-4415.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TIR domain-containing adapter-inducing beta interferon (TRIF) mediates immunological memory against bacterial pathogens
AU - Kanagavelu, Saravana
AU - Flores, Claudia
AU - M. Termini, J.
AU - Romero, Laura
AU - Riveron, Reldy
AU - Ruiz, Jose
AU - Arditi, Moshe
AU - Schesser, Kurt
AU - Fukata, Masayuki
PY - 2015
Y1 - 2015
N2 - 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 (Mπs) 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. TRIFdependent 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.
AB - 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 (Mπs) 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. TRIFdependent 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.
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U2 - 10.1128/IAI.00674-15
DO - 10.1128/IAI.00674-15
M3 - Article
VL - 83
SP - 4404
EP - 4415
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 11
ER -