Date of Completion
Spring 5-1-2025
Project Advisor(s)
Steven Szczepanek; Clinton Mathias; Steven Geary
University Scholar Major
Pathobiology
Disciplines
Immunology and Infectious Disease | Immunology of Infectious Disease | Life Sciences
Abstract
No vaccine exists for Mycoplasma pneumoniae (Mp) infections, largely due to the
gap in understanding in the virulence and immunopathogenesis of this bacterium.
We have recently demonstrated that neutrophils are maladaptive in the context of
Mp infection, and drive disease severity while also impairing bacterial clearance.
Furthermore, we observed that B cells play a regulatory role in limiting disease
severity by modulating neutrophilic inflammation. We investigated this
phenomenon further to elucidate the mechanisms by which B cells regulate
neutrophilic inflammation. We utilized a monoclonal antibody to deplete B cells
during Mp infection and found that B-cell-depleted mice had elevated neutrophil
numbers in the airways compared to B-cell-sufficient controls, indicating
exacerbated suppurative pneumonia. We phenotyped airway inflammation via
flow cytometry and found an accumulation of Fas+ neutrophils in the airways of B-
cell-depleted mice; a population absent in controls. We observed no differences in
other assessed death receptors (TNF-R1, TRAIL-R, and PD-1). These data indicate
that B cells may regulate neutrophilia via the Fas/FasL pathway. Indeed, using a
flow-cytometric based Annexin V assay, we found that greater than 70% of Fas-
expressing neutrophils in Mp infected mice are apoptotic – and a small population
of B-cells appear to provide the FasL ligand. Collectively, our data indicate that B-
cells ameliorate Mp-induced suppurative pneumonia by inducing neutrophil
apoptosis via the Fas/FasL pathway. We are currently further interrogating this
mechanism via RNAscope staining to identify spatial patterns of expression of Fas
and FasL in the lung parenchyma. Understanding this regulatory mechanism can
advance immunological research by further characterizing the function of
regulatory B cells in disease and may provide insight into regulation of neutrophils
during infection. By contributing to basic and applied immunology and
microbiology, our work has broad implications for both fields.
Recommended Citation
Velazquez, Nathan D., "Investigating Regulation of Neutrophil-mediated Inflammation in Mycoplasma pneumoniae Infection" (2025). University Scholar Projects. 104.
https://digitalcommons.lib.uconn.edu/usp_projects/104
