Michal Olszewski, D.V.M., Ph.D.
The scientific interest of our group focuses on the interface of the adaptive and innate immunity during host-pathogen interactions. Mechanisms involved in the pathogenesis of Cryptococcus neoformans infection and the persistence of this microbe are the main focus of our work. We are aslo interested in the development of protective responses against fungal and bacterial pathogens. We study the interplay between host and microbial factors in different aspects of the host response to this pathogenic yeast including T cell polarization, activation of innate immune cells (macrophages and dendritic cells), cytokine signaling, changes in leukocyte activation patterns, and control of dissemination of this pathogen from lungs into the CNS.
Our most recent studies focus on epigenetic mechanisms in TNFa induced dendritic cell stabilization and their role in generation and sustenance of protective immune response and studies of CNS inflammatory responses using fungal CNS dissemination model.
Davis MJ, Eastman AJ, Qiu Y, Gregorka B, Kozel TR, Osterholzer JJ, Curtis JL, Swanson J, Olszewski, MA. Macrophage lysosome damage is a crucial component of virulence for fungal pathogen Cryptococcus neoformans. J.Immunol 2015; 194: 2219-31
Eastman AJ, He X, Qiu, Y, Davis MJ, Vedula P, LyonsDM, ParkYD; Hardison SE; Malachowski A; Wormley FL; Williamson PR, Olszewski MA. Cryptococcal Heat Shock Protein 70 Homolog Ssa1 Contributes to Pulmonary Expansion of Cryptococcus neoformans during the Afferent Phase of the Immune Response by Promoting Macrophage M2 Polarization. J Immunol. 2015 194(12):5999-6010
Qiu Y, Davis MJ, Dayrit JK, Carolan J, Osterholzer JJ, Curtis JL, Olszewski, MA. Scavenger receptor A modulates the immune response to pulmonary Cryptococcus neoformans infection. J Immunol. 2013 ;191(1):238-48;
Davis MJ, Tsang T, Dayrit JK, Qiu Y, Freij JB, Huffnagle GB, Olszewski, MA. Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection. MBio. 2013; 4(3)/mBio.00264-13
Qiu Y, Zeltzer S, Zhang Y, Wang F, Chen G, Murdock BJ, Toews GB, Bhan U, Osterholzer JJ, Standiford TJ, Olszewski, MA. Early induction of CCL7 downstream of TLR9 signaling promotes the development of robust immunity to cryptococcal infection. J. Immunol: 2012; 188:3940-8
Qiu Y, Davis MJ, Dayrit J, Hadd ZD, Meister DL, Osterholzer JJ, Williamson PR, Olszewski, MA. Immune modulation mediated by cryptococcal laccase promotes pulmonary growth and brain dissemination of virulent Cryptococcus neoformans in mice. 2012, PLoS ONE 7(10): e47853. doi:10.1371/journal.pone.0047853
He X, Lyons DM, Toffaletti DL, Zhang Y, Wang F, Qiu Y, Lee A, Dayrit J, Perfect JR, Olszewski, MA. Virulence Factors Identified by Cryptococcus neoformans Mutant Screen Differentially Modulate Lung Immune Responses and Brain Dissemination. Am J Pathol; 2012; 181:1356-66
Osterholzer JJ, Surana R, Milam JE, Montano GT, Chen GH, Sonstein J, Curtis JL, Huffnagle GB, Toews GB, Olszewski MA: Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung. Am J Pathol; 174: 932-943, 2009
Zhang Y, Wang F, Tompkins KC, McNamara A, Jain AV, Moore BB, Toews GB, Huffnagle GB, Olszewski MA: Robust Th1 and Th17 immunity supports pulmonary clearance but cannot prevent systemic dissemination of highly virulent Cryptococcus neoformans H99. Am J Pathol; 175: 2489-2500 2009