Kyungryun Kim
Research Mentor: Jane Deng
Mentor Department: VA Ann Arbor/Med-Pulmonary, Medicine
Author(s): Kyungryun Kim, Kyle Carver, John Erb-Downward, Derek Dimcheff, Jane Deng
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 82
Abstract
Background: Influenza infections are known to increase susceptibility to secondary bacterial infections, notably Streptococcus pneumoniae (Sp). Neutrophils (polymorphonuclear leukocytes, or PMNs) play a crucial role in the elimination of bacterial and fungal infections. We investigated whether neutrophils from virally infected animals clear bacteria worse than neutrophils from uninfected animals. Hypothesis: We hypothesized that neutrophils produced during influenza are less effective at clearing bacteria due to the presence of type I interferons (IFNs), a family of cytokines that inhibit viral replication. We also hypothesized that ex vivo immune stimulation by a “bacterial” stimulus would enhance their ability to eliminate bacteria. Methods: Bone-marrow-derived neutrophils from naïve or influenza-infected wild-type C57Bl/6J (B6) mice were left unstimulated or primed with a Toll-like receptor 2 (TLR2) ligand, Pam3CSK4 (P3C), which mimics a component of the cell wall of gram-positive bacteria. The Streptococcus pneumoniae serotype 23F (Sp 23F) strain of bacteria was opsonized with mouse complement, then added to neutrophils for 30 and 90 minutes. This was followed by the enumeration of bacterial colony-forming units (CFU) in supernatants and cell lysates. We then isolated neutrophils from animals deficient in type I IFN receptor signaling (IFNAR KO) and wildtype B6 animals on day 7 following flu infection and similarly examined their ability to control Sp ex vivo. Results: We observed that bacterial CFU increased in numbers from 30 to 90 minutes, and PMNs isolated from flu-infected neutrophils exhibited an impaired ability to control bacterial growth compared to PMNs from uninfected animals. We also found that P3C-stimulated neutrophils did not have enhanced bacterial control compared to unstimulated PMNs. However, following flu infection, neutrophils from IFNAR knockout animals display markedly improved control of Sp growth. Conclusions: Overall, these studies demonstrate that viral infections impair neutrophil functions against bacteria and that type I IFNs may mediate this impairment.
