This year, together with collaborators at SUNY Upstate Medical University, New York and University of Newcastle, Australia, I have contributed to two original reports describing translational advances. In the first of these studies, we examined the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators. Age-dependent diminished production of proinflammatory mediators was associated with diminished recruitment of granulocytes and reduced severity of clinical responses, including weight loss and respiratory dysfunction. The differences observed when comparing these results to those reported among elderly human subjects may be related to the specific extent of aging and its impact on biochemical and cellular inflammatory responses and/or the role of lifetime virus re-exposure on the clinical outcome from acute pneumovirus disease (Bonville et al. Virology 2007). ? ? In a second study, we explored the possibility that eosinophils play a direct role in promoting clearance of the prevalent respiratory pathogen, respiratory syncytial virus (RSV) when used in an intranasal challenge model in mice. Specifically, we found that virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice than in wild type mice. In terms of mechanism, we demonstrated that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after ssRNA stimulation of the TLR7-MyD88 pathway. Collectively, the results demonstrate that eosinophils promote virus clearance and may thus limit virus-induced lung dysfunction. (Phipps et al. Blood 2007).? ? I have also published an invited, peer-reviewed manuscript describing the pneumonia virus of mice model entitled """"""""Pneumonia virus or mice: severe respiratory virus infection in a natural host"""""""" (Immunol Lett 2008; 118: 6 - 12)

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000943-05
Application #
7732598
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$736,532
Indirect Cost
City
State
Country
United States
Zip Code
Ma, Michelle; Rice, Tyler A; Percopo, Caroline M et al. (2017) Silkworm larvae plasma (SLP) assay for detection of bacteria: False positives secondary to inflammation in vivo. J Microbiol Methods 132:9-13
Percopo, Caroline M; Ma, Michelle; Rosenberg, Helene F (2017) Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1-/- mice. J Leukoc Biol 102:905-913
Dyer, Kimberly D; Drummond, Rebecca A; Rice, Tyler A et al. (2016) Priming of the Respiratory Tract with Immunobiotic Lactobacillus plantarum Limits Infection of Alveolar Macrophages with Recombinant Pneumonia Virus of Mice (rK2-PVM). J Virol 90:979-91
Brenner, Todd A; Rice, Tyler A; Anderson, Erik D et al. (2016) Immortalized MH-S cells lack defining features of primary alveolar macrophages and do not support mouse pneumovirus replication. Immunol Lett 172:106-12
Rosenberg, Helene F; Druey, Kirk M (2016) Eosinophils, galectins, and a reason to breathe. Proc Natl Acad Sci U S A 113:9139-41
Rice, Tyler A; Brenner, Todd A; Percopo, Caroline M et al. (2016) Signaling via pattern recognition receptors NOD2 and TLR2 contributes to immunomodulatory control of lethal pneumovirus infection. Antiviral Res 132:131-40
Rosenberg, Helene F (2015) Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense. Int J Mol Sci 16:15442-55
Percopo, Caroline M; Rice, Tyler A; Brenner, Todd A et al. (2015) Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection. Antiviral Res 121:109-19
Percopo, Caroline M; Dyer, Kimberly D; Garcia-Crespo, Katia E et al. (2014) B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection. J Immunol 192:5265-72
Glineur, Stephanie F; Bowen, Aaron B; Percopo, Caroline M et al. (2014) Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFN?) gene-deleted mice. Virology 468-470:140-9

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