Degree

Doctor of Philosophy (PhD)

Department

Pathobiological Sciences

Document Type

Dissertation

Abstract

Neutrophils are the most abundant leukocytes (50% to 70%) in humans and are the first immune cell population recruited to the sites of infection. They are known to act as the first line of innate immune defense against invading pathogens, and more recently, to playing a crucial role in orchestrating adaptive immune responses. The role of neutrophils in the respiratory viral infections till date remains unclear and controversial. Previous studies demonstrated both beneficial as well as pathogenic role for neutrophils in respiratory viral infections, especially influenza.

Previous findings reported an early and high influx of neutrophils into the airways early after respiratory pneumovirus infection. Nevertheless, the role of these cells in respiratory pneumovirus induced host responses remains largely unclear. Human metapneumovirus (HMPV) and Human respiratory syncytial virus (HRSV) belong to the family Pneumoviridae, which are significant human respiratory pathogens and causing acute lower respiratory tract infection with similar clinical symptoms in the young, elderly and immune-compromised individuals.

In understanding the role of neutrophils in these infections, we used in vivo mouse models of HMPV or HRSV infection. Depletion of neutrophils during HMPV infection in mice led to increased inflammatory responses and disease outcome, proving the beneficial role of these cells during HMPV infection. On the other hand, RSV infection in neonatal mice exposed to cigarette smoke in-utero exhibited exacerbated lung pathology characterized by an increased neutrophil recruitment into the airways, suggesting a harmful role of neutrophils when recruited in excessive levels. Overall, our studies indicate that neutrophil play a key role in orchestrating host inflammatory responses during respiratory pneumovirus infection and that, a fine balance in the recruitment of neutrophils is essential during respiratory viral infection.

Date

6-4-2018

Committee Chair

Guerrero-Plata, Antonieta

Available for download on Friday, June 07, 2019

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