Role of lymphotoxin beta receptor signaling during B cell mediated protection against Toxoplasma gondii
HELLE M. 1, SORG U. 1, MOCK J. 1, KÜPPER N. 1, PRACHT K. 3, SCHAVIER S. 1, HEGEMANN J. 2, DEGRANDI D. 1, JÄCK H. 3, PFEFFER K. 1
1 Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University , Düsseldorf, Germany; 2 Institute of Functional Genome Research of Microorganisms, Heinrich-Heine University, Düsseldorf, Germany; 3 Division of Molecular Immunology, Friedrich-Alexander University, Erlangen, Germany
The lymphotoxin beta receptor (LTβR) belongs to the TNF receptor superfamily and is essential for the organogenesis of secondary lymphoid organs as well as the coordination of an effective immune response against invading pathogens. LTβR-deficient mice (LTβR-/-) exhibit a pleiotropic phenotype with immunological defects that cause increased susceptibility to pathogens such as Toxoplasma gondii (T. gondii).
T. gondii is an obligate intracellular parasite that causes toxoplasmosis in humans and virtually all warm-blooded animals. LTβR-/- mice infected with T. gondii fail to induce a potent immune response in time and succumb to the infection instead of reaching chronic stage. While cell autonomous defense mechanisms and T cell immunity against T. gondii have been investigated in the past, the role of B cell mediated protection and LTβR-signalling against this intracellular pathogen is less well understood.
Results and Conclusion
In contrast to WT animals, LTβR-/- mice do not survive acute toxoplasmosis. Passive immunization of WT and LTβR-/- mice with immune serum containing T. gondii-specific antibodies led to prolonged survival, but ultimately could not rescue LTβR-/- mice from death. Parasite burdens in spleen, lung, peritoneal exudate but not brain were increased in LTβR-/- compared to WT mice at day 9 post infection, with no significant impact of the transferred immune serum. T. gondii-specific IgM and IgG antibodies were almost not detectable in the serum of LTβR-/- compared to WT mice.
In the bone marrow, LTβR-/- mice showed an increased frequency of mature B cells compared to WT mice. Furthermore, plasma cells in LTβR-/- mice expressed predominantly IgM, whereas WT plasma cells expressed IgA. During infection, WT mice showed an almost complete loss of BM B cells which was less pronounced in LTβR-/- animals.
These results illustrate an interesting role of LTβR signalling for the B cell compartment during T. gondii infection.