Reginaldo Brito dos Santos Junior

I am a biomedical scientist with experience in immunopathology, molecular pathology, and cell biology. I have investigated parasite–host interactions in Leishmania using confocal microscopy and immunofluorescence. I also study splenic disorganization and plasmacytosis in Visceral Leishmaniasis, specifically focusing on B-cell differentiation and plasmacytosis in both an experimental hamster model and human samples. Additionally, I have participated in COVID-19 immunopathology research. Throughout my training, I have strengthened my expertise in immunohistochemistry, histological analysis, and transcriptomic data analysis.

EDUCATION

MSc in Human Pathology - Universidade Federal da Bahia (UFBA)

RESEARCH, TEACHING, or OTHER INTERESTS

Immunology and Microbiology, Histology, Infectious Diseases

Scopus Publications

Lymphocyte loss and plasmacytosis are associated with IL-6- and TNF-producing cells in the spleens of fatal COVID-19 cases
Bianca Ramos Mesquita, Lilian Verena da Silva Carvalho, Leonardo Cardoso Gomes Baqueiro, Reginaldo Brito, Luma Bahia Figueiredo Pinto, et al.
Frontiers in Cellular and Infection Microbiology, 2025
Background The spleen undergoes changes during acute and chronic infections, which may contribute to immune dysregulation and disease aggravation. In fatal cases of COVID-19, pronounced splenic changes are noted. However, the role played by these alterations in patient mortality remains poorly understood. Objectives: We aim to characterize structural alterations and changes in splenic cell populations in fatal COVID-19 cases, as a potential substrate for immune dysfunction associated with bacterial coinfection and mortality in severe infectious diseases. Methods In this study, we characterized the histological and cellular changes observed in the spleens of nine patients who died from COVID-19. Spleens from five healthy individuals were used as a reference. Histopathological analysis and immunolabeling techniques were employed to evaluate tissue architecture, cell composition, cytokine production, and cell death. Results COVID-19-associated changes included atrophy of the white pulp (WP), reduced cellular density in the red pulp (RP), and reticular fiber fragmentation. Leukocyte phenotyping revealed substantial lymphocyte depletion across all splenic compartments, accompanied by plasma cell accumulation. These alterations correlated with increased numbers of IL-6- and TNF-producing cells. Additionally, a high density of TUNEL-positive cells indicated widespread cell death in the spleens of COVID-19 patients. Conclusion These findings suggest that the spleen contributes to the inflammatory response in SARS-CoV-2 infection, acting both as a source of inflammatory cytokines as well as a site of leukocyte, particularly lymphocyte, death both in association with the exacerbated release of IL-6 and TNF.
Leishmania amazonensis infection impairs VLA-4 clustering and adhesion complex assembly at the adhesion site of J774 cells
Reginaldo Brito, Erina Masayo Hassegawa, Patrick Camardelli, Kalene Elpídio, Juliana de Menezes, et al.
Pathogens and Disease, 2023
Cutaneous leishmaniasis is an infectious disease that may lead to a single or multiple disseminated cutaneous lesions. The mechanisms involved in Leishmania dissemination to different areas of the skin and the internal organs remain poorly understood. Evidence shows that Very Late Antigen-4 (VLA-4)-dependent phagocyte adhesion is impaired by Leishmania infection, which may be related to the mechanisms of parasite dissemination. We investigated factors potentially associated with decreased VLA-4-mediated adhesion in Leishmania-infected macrophages, including lipid raft-mediated VLA-4 mobilization along the cellular membrane, integrin cluster formation at the cell base (adhesion site), and focal adhesion complex assembly. Phagocytes treated with Methyl-β-Cyclodextrin (MβCD) demonstrated reduced adhesion, similarly to Leishmania amazonensis-infected J774 cells. Infected and MβCD-treated macrophages presented decreased VLA-4 mobilization to the adhesion plane, as well as reduced integrin clustering. Leishmania amazonensis-infected cells exhibited talin depletion, as well as a decreased mobilization of adhesion complex proteins, such as talin and viculin, which were associated with lower VLA-4 concentrations at the adhesion site and limited cell-spreading. Our results suggest that Leishmania infection may modulate the firm adhesion phase of the cell-spreading process, which could contribute to the bloodstream dissemination of infected cells.
COVID-19 beyond DAD: Persisting microcirculation thrombosis, hidden infections, and early pulmonary fibrosis as remaining challenges of the disease
Lilian V.S. Carvalho, Cassiana da Silva Souza, Jonathan L.M. Fontes, Lara Cardoso, Milton Salomar, et al.
Human Pathology Reports, 2022
Anti-leishmania infantum antibody-producing plasma cells in the spleen in canine visceral leishmaniasis
Jonathan L. M. Fontes, Bianca R. Mesquita, Reginaldo Brito, Juliana C. S. Gomes, Caroline V. B. de Melo, et al.
Pathogens, 2021
The spleen is involved in visceral leishmaniasis immunopathogenesis, and presents alterations in white-pulp microenvironments that are associated with an increased susceptibility to coinfections and patient death. Plasmacytosis in splenic red pulp (RP) is one observed alteration, but the specificity of antibody-secreting cells and the distribution of them has not yet been evaluated. We biotinylated soluble L. infantum membrane antigens (bSLMA) used as probes in modified immunohistochemistry, and detected the presence of anti-L. infantum antibody-secreting cells. Were used spleens from eight dogs from the endemic area for canine visceral leishmaniasis (CanL), and three healthier controls. The spleen sections were cryopreserved, and we performed modified immunohistochemistry. The ratio of plasma cells which were reactive to bSLMA (Anti-Leish-PC) in the spleen RP and periarteriolar lymphatic sheath (PALS) were calculated. Dogs with CanL present hyperglobulinemia and more plasma cells in their RP than the controls. Furthermore, dogs with CanL presented a lower proportion of Anti-Leish-PC in their RP than in PALS. Likewise, dysproteinemia was related to RP and PALS plasmacytosis, and a more severe clinical profile.
Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
Caroline Vilas Boas de Melo, Felipe Guimarães Torres, Micely D’El-Rei Hermida, Jonathan L. M. Fontes, Bianca Ramos Mesquita, et al.
Frontiers in Immunology, 2021
Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused byLeishmaniaspp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreasedDLK1expression. The expression ofCXCL13, CCR5, CCL19, CCR6, CCR7andLTAdecreased, likely regulated byCDKN2Aoverexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.

Publications

FREITAS, LUIZ A. R. ; CARVALHO, LILIAN V. S. ; FONTES, JONATHAN L. M. ; SOUZA, CASSIANA S. ; SANTOS, REGINALDO B. ; CARDOSO, LARA T. ; FIGUEIRA, CLAUDIO P. ; FONSECA NETO, MILTON S. ; DIAS, RAFAEL C. M. F. ; SOLCÀ, MANUELA S. ; GONÇALVES, MARILDA S. ; YAHOUEDEHOU, SETONDJI C. M. A. ; NUNES, CEUCI L. X. ; OLIVEIRA, GERALDO G. S. ; DOS'SANTOS, WASHINGTON L. C. . Vaso-occlusive crisis in a patient with sickle cell trait and COVID-19. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v. 25, p. 10318-10320, 2021.

GRANT DETAILS

Doctorate productivity scholarship: Coordenação de Aperfeicoamento de Pessoal de Nível Superior – CAPES (2023-present)