Atrophy of mesenteric lymph nodes in experimental Chagas' disease: differential role of Fas/Fas-L and TNFRI/TNF pathways.
It is currently accepted that experimental acute infection by Trypanosoma cruzi promotes changes in secondary lymphoid organs, with general T and B lymphocyte polyclonal activation. Here we show that mesenteric lymph nodes (MLN) of acutely infected mice show severe atrophy due to extensive lymphocyte apoptosis. Accordingly, clusters of apoptotic cells are detected in the initial phase of infection in MLN but not in subcutaneous nodes. Moreover, such atrophy is independent of the infection route, parasite load or the mouse strain used. Studies in Fas-L deficient (BALB gld/gld+/+) and in TNF type 1 receptor (p55-/-) knockout mice indicate that both molecules are involved in MLN atrophy: Fas-L participates in cell death of CD4+ as well as B lymphocytes, whereas the TNF type 1 receptor is important for the apoptosis of CD4+ and CD8+ T lymphocytes. In contrast, perforin does not play a role, as lymph nodes from perforin-deficient mice do not behave differently from the corresponding wild types. Our data support the concept that, even in a systemic infection, differential (even opposing) responses can be found in different lymph node chains.
de Meis
Juliana
J
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Ave. Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil.
Mendes-da-Cruz
Daniella Arêas
DA
Farias-de-Oliveira
Désio Aurélio
DA
Corrêa-de-Santana
Eliane
E
Pinto-Mariz
Fernanda
F
Cotta-de-Almeida
Vinícius
V
Bonomo
Adriana
A
Savino
Wilson
W
D000818:Animals; D017209:Apoptosis; D001284:Atrophy / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D014355:Chagas Disease / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D017353:Gene Deletion; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D052899:Pore Forming Cytotoxic Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D019014:fas Receptor
D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor; C483886:perforin, mouse