Infectious diseases, immunity, and host-pathogen interactions 

Our research interests center on understanding the immune responses induced by infection, host-pathogen interactions, and the development of vaccines and therapeutics to protect humans against infection and infectious disease. We use animal models of infectious diseases to investigate the immune responses elicited by infection, the protective mechanisms, disease progression, pathogen pathogenesis as well as host-pathogen interactions. 

Currently, we have two major research focuses:

(1) The immunomodulatory roles of helminth infection

It is known that helminth infection can modulate host immune responses that affect the host's susceptibility to diseases or subsequent microbial infection. However, the impacts on the disease outcomes were highly diverse and controversial. 

In contrast to the majority of the literature suggesting helminth infection increases the host's susceptibility to subsequent unrelated infections, we discovered that prior helminth infection resulted in enhanced protection, evidenced by increased survival rate and decreased bacterial burden. Our data revealed that helminth-mediated immunomodulatory effects could provide a survival advantage to subsequent unrelated infections. We are using established animal models to investigate the underlying mechanisms.

(2) The Reality of “Virtual Memory” CD8 T cells (CD8 Tvm)  

Immunological memory cells have traditionally been thought to be generated by previous antigen exposure. Recently, populations of "antigen-inexperienced innate memory" CD8 T cells have been described. These cells display distinct phenotypic and functional properties that resemble antigen-experienced "true memory" CD8 T cells, yet they arise naturally in naïve and germ-free mice without exposure to foreign antigens. They have both innate-like and memory-like characteristics. We found that one of these populations, called "virtual memory" CD8 T (CD8 Tvm) cells, underwent robust expansion after helminth infection. We showed that CD8 Tvm cells expanded upon helminth infection are sufficient to provide innate non-cognate “collateral/bystander” protection against irrelevant bacterial infection. We are investigating the functions, protective mechanisms, origin, development, and fate of these CD8 Tvm cells to gain a better and thorough understanding of this unique population, which will be the key to harnessing the innate-like as well as memory-like characteristics of CD8 Tvm cells to explore their potential to fight against infection and cancer.

1. Smiley, S.T., F. M. Szaba, L. W. Kummer, D. K. Duso, and J. S. Lin*. 2019. Yersinia pestis Pla protein thwarts T cell defense against plague. Infect Immun. (In Press)  
2. Lin, J.S.*, K. Mohrs, F. M. Szaba, L. W. Kummer, E. A. Leadbetter, and M. Mohrs*. 2019. Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection. Mucosal Immunol. 2019 Jan;12(1):258-264. 
3. Szaba, F.M., M. Tighe, L. W. Kummer, K. G. Lanzer, J. M. Ward, P. Lanthier, I. J. Kim, A. Kuki, M. A. Blackman, S. J. Thomas and J. S. Lin*. 2018. Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection. PLOS Pathogens. 2018 April, 14 (4): e1006994. 
4. Blackman, M.A.*, I. J. Kim, J. S. Lin, and S. J. Thomas. 2018. Challenges of Vaccine Development for Zika Virus. Viral Immunol. 2018, 31 (2):117-123.
5. Szaba, F.M., L. W. Kummer, D. K. Duso, E.P. Koroleva, A. V. Tumanov, A. M. Cooper, J. B. Bliska, S. T. Smiley, and J. S. Lin*. 2014 May. TNFa and IFNg but not perforin are critical for CD8 T cell-mediated protection against pulmonary Yersinia pestis infection. PLOS Pathogens. 2014 May, 10 (5): e1004142.