<p>Despite the advanced knowledge of the mechanisms of influenza infection and improved vaccines, Influenza A Virus still causes a life-threatening respiratory disease, especially during pandemics. Past investigations have proposed a synergism between Influenza A virus and a simultaneous or subsequent bacterial superinfection as the predominant cause of death. The recent development of animal models to study these heterologous infections has shed light onto the diverse mechanisms by which Influenza A Virus may increase the susceptibility to contract a secondary bacterial infection. These studies suggested an important role for the innate immune system in mediating such disease. We developed a model of heterologous infection combining Influenza A Virus and <em>Bordetella parapertussis</em> that demonstrated a critical role for MIP-2 to drive pulmonary neutrophilia in the pathology associated with bacterial superinfection of influenza. However, the origin of this increased MIP-2 production and the mechanisms underlying the immunopathology remained to be elucidated. The present studies proposed IL-1β overproduction as the upstream cause of the increased MIP-2 production observed in heterologous infection. This exaggerated IL-1β production was likely related to the increased bacterial burden observed in heterologously infected mice. This study also demonstrated that reduction in IL-1β production by blockade of the inflammasome seemed to provide an improvement in the clinical symptoms and the immunopathology of the disease. Thus, interventions to attenuate the exacerbated bacterial burden and the inflammatory responses derived from the subsequent IL-1β overproduction should be further investigate as possible therapeutic approaches to treat bacterial superinfections.</p> / Master of Science (MSc)

Bats are crucial to ecological function and provide key ecosystem services to people but face a variety of significant threats. One current threat to North American bats is white-nose syndrome (WNS), a disease caused by the invasive fungal pathogen Pseudogymnoascus destructans (Pd) that has killed millions of hibernating bats across the continent. Remnant populations of affected bat species persist but are so depleted that they may now be highly vulnerable to new threats, or to the synergistic effects of multiple existing threats. The emergence of novel or opportunistic pathogens in bat hosts is a particular concern for the survival of these small, isolated colonies. Apart from studies of WNS and zoonotic pathogens of humans, however, bat diseases remain poorly understood. In this paper, I describe the pathology of a new, highly aggressive bat disease affecting hibernating little brown myotis (Myotis lucifugus) and identify candidate microbes as possible causative agents. The pathological signs that were observed diverged from those of WNS, and included blue fluorescence in the wings when trans-illuminated with ultraviolet light, and the rapid development of wing necroses and mortality within weeks of the onset of hibernation. Pathology, wing swab cultures, post-mortem analyses, and hemolysis testing identified an array of candidate species, but suggest that a possible cause is a polymicrobial infection involving two etiological agents – Trichosporon yeast and Serratia bacteria. Both species have been documented as part of the mycobiota and microbiota of healthy bats, and cave environments. They are also opportunistic pathogens, known to cause infection in other wild animals and immunocompromised humans. Opportunistic pathogens have been increasingly implicated as a cause of mass mortality events in wildlife. The disease identified here has, to my knowledge, not previously been described, and could represent a new threat to North American bats, compounding concerns for populations facing an already precarious situation. / Biology