Development of fatal intestinal inflammation in MyD88 deficient mice co-infected with helminth and bacterial...

Area of Science:

• Immunology
• Microbiology
• Parasitology

Background:

• Intestinal helminth and bacterial infections pose significant global health risks, particularly for children.
• Enteropathogenic bacteria and helminth parasites can co-exist, potentially altering host immune responses.

Purpose of the Study:

• To investigate the role of the MyD88 signaling pathway in host defense during co-infection with the helminth Heligomosomoides polygyrus and the bacterial enteropathogen Citrobacter rodentium.
• To determine how helminth infection impacts the response to bacterial pathogens via the MyD88-dependent Toll-like receptor (TLR) signaling pathway.

Main Methods:

• Utilized MyD88 knockout and wild-type C57BL/6 mice.
• Infected mice with H. polygyrus, C. rodentium, or both pathogens concurrently.
• Assessed levels of intestinal inflammation, mortality, phagocyte recruitment, chemoattractant expression (KC), bacterial translocation, and antimicrobial peptide expression.

Main Results:

• MyD88 knockout mice co-infected with H. polygyrus and C. rodentium exhibited exacerbated intestinal inflammation and higher mortality rates compared to wild-type controls.
• Enhanced susceptibility in co-infected MyD88 knockout mice was linked to reduced phagocyte recruitment, decreased KC expression, and increased bacterial translocation.
• A significant downregulation of antimicrobial peptide expression was observed in the intestinal tissue of co-infected MyD88 knockout mice, correlating with increased bacterial infection severity.

Conclusions:

• The MyD88 signaling pathway is essential for effective host defense and survival during combined helminth and enteric bacterial co-infections.
• Disruption of MyD88-dependent signaling pathways compromises the immune system's ability to control bacterial pathogens in the presence of helminth co-infection.