Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis.

Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT)-α, LT-ß, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-ß, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02) in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4) compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01). These changes in the spleen were associated with higher frequency of severe disease (7/12) in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01) splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis.

Experimental chronic Chagas' disease myocarditis is an autoimmune disease preventable by induction of immunological tolerance to myocardial antigens.

The protozoan Trypanosoma cruzi causes chronic Chagas' disease myocarditis (CCDM) in infected mammals. The pathogenesis of CCDM, however, is still unclear. Indirect evidence for either parasite- or heart-specific immune responses playing a pathogenic role is available. In this work, the participation of autoimmunity in the development of CCDM is demonstrated in mice in which immunological tolerance to heart antigens was induced or strengthened prior to their infection by T. cruzi. Tolerance was induced by heart antigen administration in the presence of complete Freund's adjuvant and anti-CD4 antibodies. Tolerized mice developed less intense CCDM than control non-tolerized animals that had received only anti-CD4 and adjuvant. This result confirms the important notion that tolerance to self, and in particular to heart antigens, may be reinforced/induced in normal animals, and raises the possibility that analogous interventions may prevent the development of CCDM in millions of T. cruzi -infected human beings.