Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.

Area of Science:

• Immunology
• Parasitology
• Microbiology

Background:

• Low-dose Trichuris muris infection induces Th1 responses, while high-dose infection induces Th2 responses in mesenteric lymph nodes (MLN).
• Classical dendritic cells (cDC) infiltrate the gut mucosa and MLN during T. muris infection.
• The specific roles of cDC subsets in orchestrating adaptive immunity to T. muris remain largely uncharacterized.

Purpose of the Study:

• To elucidate the distinct roles of IRF4-dependent and IRF8-dependent classical dendritic cell subsets in the induction of adaptive immune responses during T. muris infection.
• To investigate the impact of cDC subset deficiencies on host parasite clearance and cytokine profiles.

Main Methods:

• Utilized genetically modified mice with deficiencies in specific cDC subsets (IRF4-dependent cDC, IRF8-dependent cDC, and combined deficiency).
• Administered low- and high-dose Trichuris muris infections to these mouse models.
• Assessed parasite burden, adaptive immune responses (Th1/Th2 cytokine production), and host survival.

Main Results:

• Mice lacking IRF4-dependent cDC exhibited impaired Th2 responses and failed to clear high-dose T. muris infections.
• Mice lacking IRF8-dependent cDC showed impaired Th1 responses but enhanced Th2 responses, clearing low-dose infections.
• Mice deficient in both IRF4- and IRF8-dependent cDC could mount a Th2 response and clear low-dose infections.

Conclusions:

• IRF4- and IRF8-dependent cDC subsets function antagonistically in regulating adaptive immunity during T. muris infection.
• Intestinal Th2 responses to T. muris can be effectively generated independently of IRF4-dependent cDC.
• These findings highlight the critical, context-dependent roles of distinct cDC populations in host defense against parasitic helminths.