Morphophysiological changes in the splenic extracellular matrix of Leishmania infantum-naturally infected dogs is associated with alterations in lymphoid niches and the CD4+ T cell frequency in spleens
Authors: Aurea Virginia Andrade da Silva
Rodrigo Caldas Menezes
Luisa Helena Monteiro de Miranda
Fabiano Borges Figueiredo
Fernanda Nazaré Morgado
Elisa Cupolillo
Renato Porrozzi
Arthur Augusto Mendes-Junior
Journal: PLoS Neglected Tropical Diseases (2018)
Discipline: IMMUNOLOGY
Keywords: spleen; canine visceral leishmaniasis; splenic white pulp; immunosuppression; parasite load
Affiliations: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil., Graduate student of the Masters Program in Cellular and Molecular Biology, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil., Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract:  The spleen is one of the main affected organs in canine visceral leishmaniasis (CVL). Disorganization of the splenic white pulp (SWP) has been associated with immunosuppression and disease progression. This study aims to assess structural and cellular changes in the splenic extracellular matrix of dogs with CVL, correlating these changes with the parasite load and clinical signs. Splenic fragments were collected from 41 naturally infected animals for parasite load quantification by quantitative PCR, histopathological analysis and immunohistochemistry for CD3+, CD4+, and CD8+ T cells; CD21+ B cells; Ki-67+, IFN-γ+, and IL-10+ cells; and the MMP-9 and ADAM-10 enzymes. Laminin, collagen and fibronectin deposition were also evaluated. The animals were grouped according to the level of SWP organization. SWP disorganization was accompanied by a reduction in the quantity of lymphoid follicles/mm2 (p &gt; 0.0001). Animals with moderate to intense SWP disorganization showed more clinical signs (p = 0.021), higher laminin (p = 0.045) and collagen deposition (p = 0.036), higher MMP-9 expression (p = 0.035) and lower numbers of CD4+ T cells (p = 0.027) in the spleen than the animals with organized SWP. These data suggest that splenic structure and function are drastically altered and compromised during CVL. 

Retracted: Yes

PubPeer comments:
 Figure 2. * Several panels appear to show unexpected duplicated (or even triplicated) areas,. I marked some of those - but not all - with boxes of the same color and shape. ![file] , 
 16 Feb 2022 retraction. https: journals.plos.org plosntds article?id=10.1371 journal.pntd.0010225 After this article [1] was published, concerns were raised about regions of similarity within the microscopy images in Fig 2. Specifically: There appear to be similarities between adjacent regions within the bottom right corner in Fig 2A. There appear to be similarities between several regions within Fig 2C. There appear to be similarities between several regions within Fig 2F. There appear to be similarities between several regions within Fig 2G. A set of underlying images for panels A-M of Fig 2 were provided. Editorial assessment of the provided data identified additional concerns that some features shown in the underlying images for Fig 2E and 2H do not appear to be present in the corresponding published figure panels. In response to queries about this figure, the corresponding author has indicated that panels within Fig 2 were altered to improve their aesthetics and to cover artifacts, and that although some modifications were improper, this does not change the final results. The corresponding author was candid and cooperative throughout the process but in light of the above issues, which raise concerns about the reliability of the reported results and data, the PLOS Neglected Tropical Diseases Editors retract this article. AVAS, RCM, LHMM, EC, RP and FNM agreed with retraction and AVAS and FNM apologize for the issues with the published article. AVAS, RP and FNM stand by the articleu2019s findings. FBF and AAM could not be reached. References 1.da Silva AVA, Figueiredo FB, Menezes RC, Mendes-Junior AA, de Miranda LHM, Cupolillo E, et al. (2018) Morphophysiological changes in the splenic extracellular matrix of Leishmania infantum-naturally infected dogs is associated with alterations in lymphoid niches and the CD4+ T cell frequency in spleens. PLoS Negl Trop Dis 12(4): e0006445. https: doi.org 10.1371 journal.pntd.0006445 pmid:29677186 ,