title: Disruption of Splenic Lymphoid Tissue and Plasmacytosis in Canine Visceral Leishmaniasis: Changes in Homing and Survival of Plasma Cells.
abstract: Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen's ability to protect against blood borne pathogens.
authors.affiliation: Fundação Oswaldo Cruz - BA, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.
authors.forename: Joselli
authors.initials: J
authors.lastname: Silva-O'Hare
authors.affiliation: Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Isabela Silva
authors.initials: IS
authors.lastname: de Oliveira
authors.affiliation: Fundação Oswaldo Cruz - BA, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.
authors.forename: Thaís
authors.initials: T
authors.lastname: Klevorn
authors.affiliation: Fundação Oswaldo Cruz - BA, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.
authors.forename: Valter A
authors.initials: VA
authors.lastname: Almeida
authors.affiliation: Fundação Oswaldo Cruz - BA, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.
authors.forename: Geraldo G S
authors.initials: GG
authors.lastname: Oliveira
authors.affiliation: Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Ajax M
authors.initials: AM
authors.lastname: Atta
authors.affiliation: Fundação Oswaldo Cruz - BA, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.|Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Luiz Antonio R
authors.initials: LA
authors.lastname: de Freitas
authors.affiliation: Fundação Oswaldo Cruz - BA, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.
authors.forename: Washington L C
authors.initials: WL
authors.lastname: Dos-Santos
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D053264:B-Cell Activating Factor / Q000096:biosynthesis; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D004283:Dog Diseases / Q000469:parasitology*; D004285:Dogs; D006942:Hypergammaglobulinemia / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D018314:Leishmania infantum / Q000235:genetics / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000469:parasitology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D010950:Plasma Cells / Q000276:immunology*; D012709:Serum Albumin / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000096:biosynthesis
chemical_list: D000913:Antibodies, Protozoan; D053264:B-Cell Activating Factor; D054377:Chemokine CXCL12; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012709:Serum Albumin; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13