Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial...

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Host defense against attaching-and-effacing bacteria relies on interleukin-23 (IL-23) and IL-22 for mucosal immunity.
• While innate lymphoid cells (ILCs) produce IL-22, the source of IL-23 during infection remains unidentified.

Purpose of the Study:

• To identify the specific source of IL-23 crucial for host defense against Citrobacter rodentium infection.
• To elucidate the role of classical dendritic cells (cDCs) in IL-23 production and immune response.

Main Methods:

• Genetic depletion of specific classical dendritic cell (cDC) subsets in mice.
• Analysis of immune responses following infection with the attaching-and-effacing bacterium Citrobacter rodentium.
• Investigation of the role of the signaling receptor Notch2 and transcription factor Batf3 in cDC differentiation.

Main Results:

• Notch2 signaling is essential for the terminal differentiation of intestinal CD11b(+) cDCs.
• Notch2-dependent CD11b(+) cDCs are the primary source of IL-23 required for survival during C. rodentium infection.
• Batf3-dependent CD103(+) cDCs do not contribute to IL-23 production in this context.

Conclusions:

• Intestinal CD11b(+) cDCs play a nonredundant role in host defense against C. rodentium by producing IL-23.
• This study clarifies a critical cellular source of IL-23 in mucosal immunity, highlighting Notch2-dependent cDCs.
• The findings underscore the specialized functions of distinct cDC subsets in orchestrating protective immune responses.