Date of Award
Master of Science (MS)
Pathology & Microbiology
Dr. Keer Sun
Secondary bacterial infections following influenza can lead to poor clinical outcomes and mortality. It is widely accepted that susceptibility to secondary bacterial infections is attributable to a suppressed innate antibacterial immunity. In contrast, a dysregulated host inflammatory response may also contribute to disease severity. Inflammation induced by viral infection alone significantly affects lung pathology, potentially exacerbating the destruction of the respiratory tract. Interestingly, the role of inflammatory mediators such as inflammatory monocytes have been extensively studied during influenza infection alone; however, their role during secondary bacterial infection are still not fully established. The objective of this study was to analyze the contribution of inflammatory monocytes during secondary S. aureus infection and their effect on lung pathology.
Based on the negative impact of inflammatory monocytes during influenza infection alone, and their little recruitment during S. aureus infection alone, we hypothesized that inflammatory monocytes contribute to increased mortality and lung pathology during secondary MRSA pneumonia. In order to study the possible effects of inflammatory monocytes, we developed post-influenza MRSA pneumonia murine models, with and without antibiotic treatment, using mice deficient in the chemokine receptor, C-C chemokine receptor type 2 (CCR2). Interestingly, we found that CCR2-deficient (CCR2-/-) mice, which are unable to sufficiently recruit inflammatory monocytes to the airways, survive significantly better compared to WT mice after post-influenza MRSA infection. Furthermore, we show, mechanistically, that inflammatory monocytes may impair the phagocytic bacterial killing function of alveolar macrophages, leading to decreased bacterial clearance and increased mortality. Future studies will evaluate the effect of inflammatory monocytes on lung damage during post-influenza MRSA pneumonia.
Fischer, Karl J., "The Role of Inflammatory Monocytes in Post-Influenza Methicillin-Resistant Staphylococcus aureus Pneumonia" (2016). Theses & Dissertations. 143.