The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS
Abstract Background Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hyperspl...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-024-06151-6 |
| _version_ | 1797259471337029632 |
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| author | Luis Gustavo Cavalcante Reinaldo Raimundo José Cunha Araújo Júnior Thiago Melo Diniz Rafael de Deus Moura Antônio José Meneses Filho Caio Victor Verçosa de Macedo Furtado Washington Luis Conrado dos Santos Dorcas Lamounier Costa Kelsen Dantas Eulálio Gabriel R. Ferreira Carlos Henrique Nery Costa |
| author_facet | Luis Gustavo Cavalcante Reinaldo Raimundo José Cunha Araújo Júnior Thiago Melo Diniz Rafael de Deus Moura Antônio José Meneses Filho Caio Victor Verçosa de Macedo Furtado Washington Luis Conrado dos Santos Dorcas Lamounier Costa Kelsen Dantas Eulálio Gabriel R. Ferreira Carlos Henrique Nery Costa |
| author_sort | Luis Gustavo Cavalcante Reinaldo |
| collection | DOAJ |
| description | Abstract Background Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. Methods From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients’ complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. Results CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = −0.71, P = 0.015). Conclusions This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages. Graphical Abstract |
| first_indexed | 2024-04-24T23:09:57Z |
| format | Article |
| id | doaj.art-0a0810dc5e634188be760a304b45bca5 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-04-24T23:09:57Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-0a0810dc5e634188be760a304b45bca52024-03-17T12:17:07ZengBMCParasites & Vectors1756-33052024-03-011711810.1186/s13071-024-06151-6The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDSLuis Gustavo Cavalcante Reinaldo0Raimundo José Cunha Araújo Júnior1Thiago Melo Diniz2Rafael de Deus Moura3Antônio José Meneses Filho4Caio Victor Verçosa de Macedo Furtado5Washington Luis Conrado dos Santos6Dorcas Lamounier Costa7Kelsen Dantas Eulálio8Gabriel R. Ferreira9Carlos Henrique Nery Costa10University Hospital of the Federal University of PiauíHospital Getúlio VargasUniversity Hospital of the Federal University of PiauíUniversity Hospital of the Federal University of PiauíDepartment of Community Medicine, Federal University of PiauíDepartment of Community Medicine, Federal University of PiauíOswaldo Cruz Foundation, Gonçalo Moniz InstituteMaternal and Child Department, Federal University of PiauíInstituto de Doenças Tropicais Natan PortellaDepartment of Microbiology-Infectious Disease and Immunology, Faculty of Medicine, University LavalDepartment of Community Medicine, Federal University of PiauíAbstract Background Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. Methods From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients’ complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. Results CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = −0.71, P = 0.015). Conclusions This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages. Graphical Abstracthttps://doi.org/10.1186/s13071-024-06151-6Visceral leishmaniasisKala-azarLeishmania infantumHypersplenismAIDST-lymphocytes |
| spellingShingle | Luis Gustavo Cavalcante Reinaldo Raimundo José Cunha Araújo Júnior Thiago Melo Diniz Rafael de Deus Moura Antônio José Meneses Filho Caio Victor Verçosa de Macedo Furtado Washington Luis Conrado dos Santos Dorcas Lamounier Costa Kelsen Dantas Eulálio Gabriel R. Ferreira Carlos Henrique Nery Costa The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS Parasites & Vectors Visceral leishmaniasis Kala-azar Leishmania infantum Hypersplenism AIDS T-lymphocytes |
| title | The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS |
| title_full | The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS |
| title_fullStr | The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS |
| title_full_unstemmed | The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS |
| title_short | The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS |
| title_sort | spleen is the graveyard of cd4 cells in patients with immunological failure of visceral leishmaniasis and aids |
| topic | Visceral leishmaniasis Kala-azar Leishmania infantum Hypersplenism AIDS T-lymphocytes |
| url | https://doi.org/10.1186/s13071-024-06151-6 |
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