Microbiota regulate innate immune signaling and protective immunity against cancer

Changsheng Xing1, Mingjun Wang2, Adebusola A Ajibade2

  • 1Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.

Cell Host & Microbe
|April 24, 2021
PubMed

Insights

Loss of TAK1 in myeloid cells alters gut microbiota, conferring resistance to colitis and colorectal cancer. Specific bacteria, like Odoribacter splanchnicus, drive protective immunity via Th17 cell induction.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Gut microbiota critically influence host immunity in colitis and colorectal cancer (CRC).
  • Mechanisms by which microbiota generate protective immunity against these diseases remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the transforming growth factor-beta-activated kinase 1 (TAK1) in myeloid cells on host immunity and disease resistance.
  • To identify microbial alterations and immune pathways conferring protection against colitis and CRC.

Main Methods:

  • Utilized myeloid-specific TAK1-deficient (Tak1ΔM/ΔM) mice resistant to chemical-induced colitis and CRC.
  • Administered antibiotics to disrupt microbiota and performed microbiota transfer experiments.
  • Analyzed immune cell populations (Th17) and cytokine signaling (IL-1β, IL-6).
  • Identified specific bacterial species, including Odoribacter splanchnicus, through 16S rRNA sequencing.

Main Results:

  • Tak1ΔM/ΔM mice exhibited complete resistance to colitis and CRC, mediated by altered gut microbiota.
  • Antibiotic treatment abrogated protection, while microbiota transfer conferred resistance.
  • Altered microbiota promoted IL-1β and IL-6 signaling, essential for Th17 cell induction.
  • Odoribacter splanchnicus abundance in Tak1ΔM/ΔM mice was sufficient to induce Th17 cells and confer resistance.

Conclusions:

  • Loss of TAK1 in myeloid cells reshapes the gut microbiota to induce protective immunity against colitis and CRC.
  • Odoribacter splanchnicus is a key bacterial species driving Th17 cell-mediated resistance.
  • These findings reveal specific microbial and immune mechanisms crucial for host defense.

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