A Brucella virulence factor targets macrophages to trigger B-cell proliferation

Area of Science:

• Immunology
• Microbiology
• Pathogen Biology

Background:

• Brucella spp. and Trypanosoma cruzi are intracellular pathogens causing chronic infections.
• Both pathogens evade host immune responses using similar strategies.
• Virulence factors like Brucella's prpA and T. cruzi's tcPrac induce B-cell proliferation, aiding chronic infection establishment.

Purpose of the Study:

• To investigate the mechanism of virulence factor action in Brucella and Trypanosoma cruzi.
• To identify the host cell targets and receptors involved in pathogen-induced B-cell proliferation.
• To determine if this virulence strategy is conserved between bacterial and protozoan pathogens.

Main Methods:

• In vitro cell culture experiments using macrophages and B-cells.
• Cytoplasmic translocation assays for Brucella's PrpA.
• Identification of host cell receptors using biochemical and genetic approaches.
• Comparative analysis of virulence factor function in Brucella and Trypanosoma cruzi.

Main Results:

• Brucella's PrpA targets macrophages and translocates to the cytoplasm.
• PrpA-treated macrophages secrete a soluble factor that induces B-cell proliferation.
• Nonmuscular myosin IIA (NMM-IIA) was identified as the host receptor for PrpA.
• The T. cruzi homologue of PrpA utilizes the same NMM-IIA receptor to induce B-cell proliferation.

Conclusions:

• Brucella and Trypanosoma cruzi pathogens employ a conserved virulence strategy involving macrophage targeting and NMM-IIA receptor engagement.
• This mechanism promotes B-cell proliferation, facilitating the chronic phase of infection for both pathogens.
• The findings reveal a shared molecular mechanism for immune evasion and chronic infection between evolutionarily distant pathogens.