Gudrun Szalay

Participation of group 2 CD1 molecules in the control of murine tuberculosis

Besides the classical major histocompatibility complex (MHC) class I and MHC class II molecules, human CD1 molecules have been shown to present mycobacterial antigens in vitro. In this study, in vivo treatment of mice with anti-CD1 monoclonal antibodies resulted in exacerbated tuberculosis at very early time points. In CD1-modulated mice, Mycobacterium tuberculosis-specific production of the type 1 cytokines, IL-12, TNF, and IFN-gamma as well as of TGF beta was reduced. These findings suggest an antigen-presenting role of CD1 molecules in tuberculosis.

Interleukin‐4 and listeriosis

Summary: Experimental infection of mice with Listeria monocytogenes (L. monocytogenes) has served as an appropriate model for analyzing Thl nil driven immune responses. Generally, Th2 responses are absent and IL‐4 is not detectable. Here, we describe experimental settings under which IL‐4 is detectable in listeriosis. Our data suggest that IL‐4 is rapidly produced after infection. This prompt IL‐4 burst seems to stimulate chemokine responses and, therefore, may participate in the regulation of the early antilisterial host response. Soon thereafter, lL‐4 production wanes. At least partially this seems to be caused by downregulation of IL‐4–producing CD4+ NK1+ TCRαβint lymphocytes by IL‐12. In the absence of IFN‐γ responsiveness, IL‐4 production is demonstrable during acquired immunity against L. monocytogenes, and this elevated IL‐4 production apparently contributes to disease exacerbation. In conclusion, the data are consistent with a detrimental role of IL‐4 in listeriosis and active control of IL‐4 synthesis by the antilisterial immune response. The rapid, but transient, IL‐4 burst in listeriosis probably contributes to host defense without impairing development of the acquired T‐cell response because of its shortness.

Functional T Cell Subsets in Mycobacterial and Listerial Infections: Lessons from Other Intracellular Pathogens

Intracellular bacteria like Mycobacterium tuberculosis, M. bovis, M. leprae, Listeria monocytogenes, Salmonella typhi, S. paratyphi and Legionella pneumophila are human pathogens. They all share the capacity to escape antibody and complement-mediated defense mechanisms afforded by the humoral immune system. The common denominator of intracellular bacteria is their capacity to invade and replicate inside mononuclear phagocytes (MPS). As long as these cells are quiescent, they provide a niche for intracellular bacteria. Once they are activated, they express potent effector functions which lead to the elimination of many bacterial invaders. Upon stimulation by cytokines, MPS express several defense mechanisms including production of defensins, acidification of the phagosome, phagosome-lysosome fusion, depletion of iron, and production of reactive oxygen and nitrogen intermediates (ROI/RNI) (Lehrer et al. 1991; Horwitz 1988; Moulder 1985; Andrew et al. 1985; Weinberg 1992; Hibbs et al. 1988; Babior 1984; Liew and Cox 1990). Together these mechanisms are part of the nonspecific host response.