Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6654220 |
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| author | Ranferi Ocaña-Guzmán Norma A. Téllez-Navarrete Lucero A. Ramón-Luing Iliana Herrera Marlon De Ita José-Luis Carrillo-Alduenda José Alberto Choreño-Parra Karen Medina-Quero Joaquín Zúñiga Leslie Chávez-Galán |
| author_facet | Ranferi Ocaña-Guzmán Norma A. Téllez-Navarrete Lucero A. Ramón-Luing Iliana Herrera Marlon De Ita José-Luis Carrillo-Alduenda José Alberto Choreño-Parra Karen Medina-Quero Joaquín Zúñiga Leslie Chávez-Galán |
| author_sort | Ranferi Ocaña-Guzmán |
| collection | DOAJ |
| description | Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy. |
| format | Article |
| id | doaj-art-fe6917520cdc4efcbb9a7741c4f486cb |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-fe6917520cdc4efcbb9a7741c4f486cb2025-08-20T02:22:34ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66542206654220Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration CapacityRanferi Ocaña-Guzmán0Norma A. Téllez-Navarrete1Lucero A. Ramón-Luing2Iliana Herrera3Marlon De Ita4José-Luis Carrillo-Alduenda5José Alberto Choreño-Parra6Karen Medina-Quero7Joaquín Zúñiga8Leslie Chávez-Galán9Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Cellular Biology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoUnit of Medical Research in Human Genetics, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, MexicoSleep Medicine Unit, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Immunology, Escuela Militar de Graduados de Sanidad, Mexico City, MexicoLaboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.http://dx.doi.org/10.1155/2021/6654220 |
| spellingShingle | Ranferi Ocaña-Guzmán Norma A. Téllez-Navarrete Lucero A. Ramón-Luing Iliana Herrera Marlon De Ita José-Luis Carrillo-Alduenda José Alberto Choreño-Parra Karen Medina-Quero Joaquín Zúñiga Leslie Chávez-Galán Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity Journal of Immunology Research |
| title | Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity |
| title_full | Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity |
| title_fullStr | Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity |
| title_full_unstemmed | Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity |
| title_short | Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity |
| title_sort | leukocytes from patients with drug sensitive and multidrug resistant tuberculosis exhibit distinctive profiles of chemokine receptor expression and migration capacity |
| url | http://dx.doi.org/10.1155/2021/6654220 |
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