Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Mast cells (MCs) are crucial immune cells at barrier tissues, responding to microbial threats.
• MCs exhibit a two-step activation mechanism integrating Toll-like receptor (TLR) sensing and type-III-secretion-system (TTSS) signals for cytokine responses to Gram-negative bacteria.
• Phenotypic heterogeneity among MC subtypes may influence their interactions with microbes.

Purpose of the Study:

• To investigate how different murine mast cell subtypes (connective-tissue MCs [CT-MCs] and mucosal MCs [M-MCs]) respond to Salmonella enterica Typhimurium (S.Tm).
• To elucidate the role of TLRs and serglycin in MC responses to S.Tm.
• To compare human LUVA MC responses to S.Tm with murine MCs.

Main Methods:

• Culturing murine MCs (IL-3 dependent and CT-MCs) and human LUVA MCs.
• Stimulating MCs with extracellular and invasive S.Tm.
• Assessing TLR expression (TLR4, TLR2, TLR2/6) and cytokine release.
• Evaluating S.Tm intracellular colonization and the role of serglycin.

Main Results:

• CT-MCs respond potently to S.Tm via two-step activation involving TLR4 and TLR2.
• M-MCs are unresponsive to extracellular S.Tm due to low TLR expression but respond to invasive bacteria.
• Serglycin in MC granules limits S.Tm colonization but does not affect cytokine release.
• Human LUVA MCs utilize a variant two-step activation combining TLR2/6 and TTSS signals.

Conclusions:

• MC subtype-specific TLR expression dictates responses to extracellular S.Tm.
• Serglycin influences bacterial intracellular survival independently of MC cytokine secretion.
• MC heterogeneity allows for differential immune responses to S.Tm infection, impacting host defense strategies.