Pasteurella multocida Toxin Manipulates T Cell Differentiation.

Area of Science:

• Immunology
• Microbial Pathogenesis

Background:

• Pasteurella multocida toxin (PMT) from serotypes A and D affects host cells by activating G proteins, altering cytoskeletal structure, and promoting cell proliferation and survival.
• PMT influences lipopolysaccharide (LPS)-induced activation in human monocytes, leading to suppressed T cell activation.

Purpose of the Study:

• To investigate the direct effects of PMT on CD4-positive T helper (Th) cells.
• To elucidate how PMT modulates Th cell differentiation and function.

Main Methods:

• Analysis of T helper cell expansion, cell cycle progression, and apoptosis following PMT treatment.
• Investigation of Th subclass differentiation by examining Signal Transducers and Activators of Transcription (STAT) family members and master transcription factors.
• Assessment of transcription factor expression (Foxp3, RORγt) and cytokine production (IL-17) in toxin-treated T cells.

Main Results:

• PMT directly amplifies Th cell expansion by enhancing cell cycle progression and suppressing apoptosis.
• PMT manipulates Th subclass differentiation, indicated by the activation of STAT family members and induction of transcription factors.
• A significant population of PMT-treated T cells co-expresses Foxp3 and RORγt, transcription factors for Treg and Th17 cells, respectively.
• Functionally, PMT-differentiated cells exhibit characteristics of inflammatory Th17 cells, producing IL-17 and promoting T cell proliferation.

Conclusions:

• PMT directly modulates T helper cell responses, promoting their proliferation and survival.
• The toxin induces a mixed Treg/Th17 transcription factor profile but functionally drives cells towards an inflammatory Th17 phenotype.
• PMT's manipulation of Th cells contributes to its pathogenic mechanisms, potentially by promoting inflammation and altering immune responses.