Manmeet Pal Singh Bhalla

Manmeet Pal Singh Bhalla, PhD, Postdoctoral Associate, Microbiology and Immunology.

Research

The overall goal of my research is to characterize age-driven changes in the host neutrophil (PMN) function during S.pneumoniae (pneumococcal) infection. I am particularly interested in identifying the changes in the transcriptome induced by pneumococcal infection in the host PMNs. This will provide insight into the signaling pathways that are critical for host response and those dysregulated in the aged population. Future work will also be aimed at transcriptomic analysis to identify S.pneumoniae genes which are up- or down-regulated in a niche- and time-specific manner during pathogenesis in mice infection model.

Pneumococcal pneumonia carries high incidence and mortality rates, especially in elderly population. Despite the availability of vaccines and antibiotics, it is increasingly becoming a nuisance in terms of hospitalization rates and treatment costs. In this context, it has become more important to shift the focus in understand the host factors which renders the host, especially the elderly group more susceptible to pneumococcal infections. Previous data showed that initial pneumococcal burden in young mice is cleared following infiltration of PMNs into the lungs. This is followed by bacterial killing by PMNs and prevention of systemic spread of the infection. However, in case of old mice, there is an initial delay in PMN infiltration in the lungs. Besides, the PMNs recruited in these old hosts display defective killing ability. This is further complicated by massive influx of neutrophils during the later stages of infection leading to host lung tissue destruction. Similar findings have been reported in elderly S.pneumoniae patients showing increased PMN infiltration in lungs with decreased bacterial killing capability. My study aims to elucidate the differences in the gene expression profiles and signaling pathways between the young and old hosts during the course of infection.

Additional data from lab has shown an important role of extracellular adenosine (EAD) pathway in pneumococcal infection. Adenosine, produced through the action of two extracellular enzymes, CD39 and CD73 was previously found to be crucial for PMN antibacterial function. Inhibition of the EAD pathway in young mice mimicked the dysregulation in PMN response and overall susceptibility to pneumococcal infection observed during ageing. My project will also aim to characterize the age-driven changes in the EAD pathway during S.pneumoniae infection.  

This work will contribute to the better understanding of host immune factors against pneumococcal infection which might facilitate improved therapeutic and/or preventive measures.

Mentor

Education

Contact

Manmeet Pal Singh Bhalla, PhD

Postdoctoral Associate

955 Main Street, Suite 5250

Phone: (716) 829-2173

Email: manmeetp@buffalo.edu