دورية أكاديمية

Contribution of Leishmania braziliensis antigen-specific CD4+ T, CD8+ T, NK and CD3+CD56+NKT cells in the immunopathogenesis of cutaneous leishmaniasis patients: Cytotoxic, activation and exhaustion profiles.

التفاصيل البيبلوغرافية
العنوان: Contribution of Leishmania braziliensis antigen-specific CD4+ T, CD8+ T, NK and CD3+CD56+NKT cells in the immunopathogenesis of cutaneous leishmaniasis patients: Cytotoxic, activation and exhaustion profiles.
المؤلفون: Cunha CF; Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Ferraz-Nogueira R; Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.; Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Costa VFA; Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.; Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Pimentel MIF; Laboratory of Surveillance for Leishmaniasis, Evandro Chagas National Institute of Infectology, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Chometon TQ; Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Lyra MR; Laboratory of Surveillance for Leishmaniasis, Evandro Chagas National Institute of Infectology, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Schubach AO; Laboratory of Surveillance for Leishmaniasis, Evandro Chagas National Institute of Infectology, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Da-Cruz AM; Laboratory of Interdisciplinary Medical Research, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil., Bertho AL; Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.; Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
المصدر: PloS one [PLoS One] 2020 Mar 23; Vol. 15 (3), pp. e0229400. Date of Electronic Publication: 2020 Mar 23 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Antigens, Protozoan/*immunology , CD4-Positive T-Lymphocytes/*immunology , CD8-Positive T-Lymphocytes/*immunology , Killer Cells, Natural/*immunology , Leishmania braziliensis/*immunology , Leishmaniasis, Cutaneous/*immunology , Leishmaniasis, Cutaneous/*pathology, Adult ; Aged ; CD3 Complex/metabolism ; CD56 Antigen/metabolism ; Cytokines/metabolism ; Female ; Humans ; Leishmaniasis, Cutaneous/parasitology ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; Young Adult
مستخلص: The pathogenesis of cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is dictated mainly by the immune-mediated-tissue inflammation developed. The understanding of the immunological mechanisms that generate tissue damage or resolution of lesions is the key to the development of effective vaccine protocols and proper therapeutic schemes. It is clear that the specific immune response mediated by T cells is responsible for the beneficial outcome of the disease, however, the roles of CD4+ T, CD8+ T, NK and NKT cell subpopulations in immunopathogenesis of CL need to be elucidated. Peripheral blood cells from patients before, during and after the antimonial therapy, as well as healthy individuals (HI) were cultured with (LbAgS) or without (NS) L. braziliensis antigens (LbAg). Afterwards, the frequencies of LbAg-specific-cytotoxic CD8+ T, CD4+ T, NK and CD3+CD56+ NKT cells, as well as their activation and exhaustion profiles, were defined by flow cytometry. We observed higher frequencies of CD8+ T, NK and CD3+CD56+ NKT cells and lower frequencies of CD4+ T lymphocytes in LbAgS cell cultures from patients before treatment. The specific response to LbAg resulted in an expansion of cytotoxic-activated CD4+ T, CD8+ T, and NK cells, before and during treatment, indicating specificity in the response by these cells against L. braziliensis. Furthermore, comparing the differences of frequencies of cytotoxic-activated CD4+T, CD8+T, and NK cells, among before and during treatment patients and HI groups, we conclude that these cell populations are in charge of immune response elicited by antimonial therapy. Interestingly, we also observed that NK cells were induced by LbAg to an exhaustion profile during all clinical stages of the disease. The increased antigen-specific activation and cytotoxic activity are in line with the strong inflammatory response described in this disease, a likely cause of tissue damage. These findings reinforce the involvement of these distinct cytotoxic-activated cell populations in the immunopathogenesis of CL, showing a character of specificity in this immune response.
Competing Interests: The authors have declared that no competing interests exist.
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المشرفين على المادة: 0 (Antigens, Protozoan)
0 (CD3 Complex)
0 (CD56 Antigen)
0 (Cytokines)
تواريخ الأحداث: Date Created: 20200324 Date Completed: 20200612 Latest Revision: 20200612
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7089553
DOI: 10.1371/journal.pone.0229400
PMID: 32203546
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0229400