Our ongoing research on the biology and function of the RNase A family of ribonucleases is focused on understanding their mechanisms of action in health and disease. In FY2018, we have expanded our study to include related T1 and T2 RNases from microorganisms as follows: Manuscript #1: Title: Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza infection. Our original objective was to explore eosinophilic inflammation and its impact on respiratory virus infection at the nasal mucosa. Interestingly and unexpectedly, A. alternata-treated mice responded to an influenza virus infection with profound weight loss and mortality compared to mice that received diluent alone (0% vs 100% survival, ***p < .001). Minimal differences in virus titer were detected, and eosinophils present in the nasal passages at the time of virus inoculation provided no protection against the lethal sequelae of disease. The lethal response was blunted when A. alternata was heat-inactivated, suggesting that the active element was in part enzymatic in nature. Among the factors that this might include, the filtrate from A. alternate includes both proteases and T1 and T2 secretory RNases that might promote lethal infection by reducing the integrity of the epithelial barrier. This hypothesis is under active investigation. Critical point: Repetitive administration of A. alternata resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza A virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. However, as increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be used for further exploration of these observations. We are considering a potential role played by fungal T1 and T2 RNases in promoting the lethal response. Ref: M Ma, JL Redes, CM Percopo, KM Druey, HF Rosenberg. 2018. Clin. Exp. Allergy 48:691-702.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Niaid Extramural Activities
Zip Code
Rosenberg, Helene F; Druey, Kirk M (2018) Modeling asthma: Pitfalls, promises, and the road ahead. J Leukoc Biol 104:41-48
Ma, M; Redes, J L; Percopo, C M et al. (2018) Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection. Clin Exp Allergy 48:691-702
Foster, Paul S; Maltby, Steven; Rosenberg, Helene F et al. (2017) Modeling TH 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunol Rev 278:20-40
Percopo, Caroline M; Brenner, Todd A; Ma, Michelle et al. (2017) SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice. J Leukoc Biol 101:321-328
Kraemer, Laura S; Brenner, Todd A; Krumholz, Julia O et al. (2017) A flow-cytometric method to evaluate eosinophil-mediated uptake of probiotic Lactobacillus reuteri. J Microbiol Methods 137:19-24
Rosenberg, Helene F; Druey, Kirk M (2016) Eosinophils, galectins, and a reason to breathe. Proc Natl Acad Sci U S A 113:9139-41
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
Yamada, Kelsey J; Barker, Tolga; Dyer, Kimberly D et al. (2015) Eosinophil-associated ribonuclease 11 is a macrophage chemoattractant. J Biol Chem 290:8863-75
Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I et al. (2014) Activated mouse eosinophils protect against lethal respiratory virus infection. Blood 123:743-52
Yang, Ming; Eyers, Fiona; Xiang, Yang et al. (2014) Expression profiling of differentiating eosinophils in bone marrow cultures predicts functional links between microRNAs and their target mRNAs. PLoS One 9:e97537

Showing the most recent 10 out of 19 publications