Survival analysis and microarray profiling identify Cd40 as a candidate for the Salmonella susceptibility locus, Ity5

Area of Science:

• Immunology
• Genetics
• Microbiology

Background:

• Salmonella Typhimurium infection outcome depends on complex immune responses in mouse models.
• Recombinant Congenic Strains (RCS) were used to identify Salmonella susceptibility loci.

Purpose of the Study:

• Identify and validate Salmonella susceptibility loci, specifically Ity5.
• Investigate the genetic and molecular mechanisms underlying Salmonella susceptibility associated with Ity5.

Main Methods:

• Screening of RCS mice for Salmonella susceptibility.
• Genetic validation of Ity5 using crosses between A/J, C57BL/6J, and 129S6 mice.
• Time-series genome-wide transcription analysis during infection.

Main Results:

• Two Salmonella susceptibility loci, Ity4 and Ity5, were identified.
• CD40 gene and associated signaling pathways showed differential expression in infected A/J mice compared to AcB60 mice.
• A/J mice exhibited impaired IgM upregulation, decreased Ig class switching, neutropenia, and reduced granulocyte recruitment.

Conclusions:

• Altered CD40 signaling is implicated in the Ity5-associated Salmonella susceptibility of A/J mice.
• Impaired granulocyte recruitment in response to infection contributes to Salmonella susceptibility.