Scientific Publications by FDA Staff

Infect Immun 2009 May;77(5):2010-21

T cells from lungs and livers of Francisella-immune mice control the growth of intracellular bacteria.

Collazo CM, Meierovics AI, De Pascalis R, Wu TH, Lyons CR, Elkins KL

Parenteral and respiratory vaccination with the intracellular bacterium Francisella tularensis have been studied using the Live Vaccine Strain (LVS) in a mouse model, and spleen cells from immune mice often used for immunological studies. However, mechanisms of host immunological responses may be different in non-lymphoid organs that are important sites of infection, such as lung and liver. Using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functions of resulting LVS-immune liver or lung cells, respectively. Surprisingly, LVS was considerably more virulent when administered by cloud aerosol compared to intranasal instillation, suggesting method-dependent differences in initial localization and/or dissemination patterns. Only low doses were sublethal, and resolution of sublethal cloud aerosol infection was dependent on IFN-gamma, TNF-alpha, and iNOS. Nonetheless, survival of cloud aerosol or parenteral infection resulted in the development of a protective immune response against lethal LVS intraperitoneal or aerosol challenge, reflecting development of systemic secondary immunity in both cases. Such immunity was further detected by directly examining the functions of LVS-immune lung or liver lymphocytes in vitro. Lung lymphocytes primed by respiratory infection, as well as liver lymphocytes primed by parenteral infection, clearly controlled in vitro intracellular bacterial growth primarily via mechanisms that were not dependent on IFN-gamma activity. Thus, our results indicate functional similarities between immune T cells residing in spleens, livers, and lungs of LVS-immune mice.