9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Unconventional Pro-inflammatory CD4 + T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice) infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4 + T cells, and mortality. The increase in TNF-producing CD4 + T cells was accompanied by a reduction in IFNγ +CD4 + T cells and a decrease of the frequency of regulatory Foxp3 +, IL-10 +, and IL17 +CD4 + T cells populations. The CD4 + T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C + cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4 + T cells from infected muMT mice presented a high frequency of CD62L hiCD44 cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4 + T cells from infected muMT mice were able to condition the CD4 + T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4 + T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4 + T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able to regulate TNF-producing CD4 + T cells since their absence favor the increase of the number of TNF + CD4 + in T. cruzi-infected mice.

          Related collections

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          Chagas disease in Spain, the United States and other non-endemic countries.

          Due to recent trends in migration, there are millions of people from Chagas disease-endemic countries now living in North America, Europe, Australia and Japan, including thousands of people with Trypanosoma cruzi infection. Most infected individuals are not aware of their status. Congenital, transfusion- and/or transplant-associated transmission has been documented in the United States, Spain, Canada and Switzerland; most instances likely go undetected. High priorities include the implementation of appropriate screening, evaluation and clinical management, and better assessment of the true burden associated with this disease. 2009 Elsevier B.V. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples.

            The aim of this study was to develop a real-time PCR technique to detect Trypanosoma cruzi DNA in blood of chagasic patients. Analytical sensitivity of the real-time PCR was assessed by two-fold serial dilutions of T. cruzi epimastigotes in seronegative blood (7.8 down to 0.06 epimastigotes/mL). Clinical sensitivity was tested in 38 blood samples from adult chronic chagasic patients and 1 blood sample from a child with an acute congenital infection. Specificity was assessed with 100 seronegative subjects from endemic areas, 24 seronegative subjects from non-endemic area and 20 patients with Leishmania infantum-visceral leishmaniosis. Real-time PCR was designed to amplify a fragment of 166 bp in the satellite DNA of T. cruzi. As internal control of amplification human RNase P gene was coamplified, and uracil-N-glycosylase (UNG) was added to the reaction to avoid false positives due to PCR contamination. Samples were also analysed by a previously described nested PCR (N-PCR) that amplifies the same DNA region as the real-time PCR. Sensitivity of the real-time PCR was 0.8 parasites/mL (50% positive hit rate) and 2 parasites/mL (95% positive hit rate). None of the seronegative samples was positive by real-time PCR, resulting in 100% specificity. Sixteen out of 39 patients were positive by real-time PCR (41%). Concordance of results with the N-PCR was 90%. In conclusion, real-time PCR provides an optimal alternative to N-PCR, with similar sensitivity and higher throughput, and could help determine ongoing parasitaemia in chagasic patients.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              T cell memory.

              Immunological memory can be defined as the faster and stronger response of an animal that follows reexposure to the same antigen. By this definition, it is an operational property of the whole animal or the immune system. Memory cells express a different pattern of cell surface markers, and they respond in several ways that are functionally different from those of naive cells. Murine memory cells are CD44 high and low in the expression of activation markers such as CD25 (IL-2R), whereas human memory cells are CD45RA-, CD45RO+. In contrast to naive cells, memory cells secrete a full range of T cell cytokines and can be polarized to secrete particular restricted patterns of secretion for both CD4 and CD8 T cells. The requirements for the activation of memory cells for proliferation and cytokine production are not quite as strict as those of naive cells, but costimulation in the broad sense is required for optimum responses and for responses to suboptimum antigen concentrations. It would appear that memory cells can persist in the absence of antigenic stimulation and persist as nondividing cells. Reencounter with the same antigen can expand the population to a new, stable, higher level and generate a separate population of CD44 high effectors that may be required for protection, while competition from other antigens can drive it down to a lower stable level. It is unclear how or where memory cells arise, but once generated they have different pathways of recirculation and homing.
                Bookmark

                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/433661
                URI : http://frontiersin.org/people/u/488919
                URI : http://frontiersin.org/people/u/461619
                URI : http://frontiersin.org/people/u/396201
                URI : http://frontiersin.org/people/u/495566
                URI : http://frontiersin.org/people/u/496152
                URI : http://frontiersin.org/people/u/19324
                URI : http://frontiersin.org/people/u/461125
                URI : http://frontiersin.org/people/u/262779
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                21 November 2017
                2017
                : 8
                : 1548
                Affiliations
                [1] 1Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , Córdoba, Argentina
                [2] 2Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University , Canberra, ACT, Australia
                Author notes

                Edited by: Emilio Luis Malchiodi, University of Buenos Aires, Argentina

                Reviewed by: Maria Bellio, Universidade Federal do Rio de Janeiro, Brazil; Jorge Raul Geffner, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina

                *Correspondence: Adriana Gruppi, agruppi@ 123456fcq.unc.edu.ar

                These authors have contributed equally to this work.

                Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2017.01548
                5702327
                28144241
                2aa995db-efb7-4695-a03f-f3af8d720d2b
                Copyright © 2017 Gorosito Serrán, Tosello Boari, Fiocca Vernengo, Beccaría, Ramello, Bermejo, Cook, Vinuesa, Montes, Acosta Rodriguez and Gruppi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 June 2017
                : 30 October 2017
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 71, Pages: 17, Words: 11332
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
                Award ID: R01AI116432-01
                Funded by: Ministerio de Ciencia, Tecnología e Innovación Productiva 10.13039/501100003033
                Award ID: Foncyt PICT 2011-2647, Foncyt PICT 2015-0645
                Funded by: Consejo Nacional de Investigaciones Científicas y Técnicas 10.13039/501100002923
                Award ID: PIP 112-20110100378
                Categories
                Immunology
                Original Research

                Immunology
                trypanosoma cruzi,chagas disease,b cell,cd4+ t cells,inflammation
                Immunology
                trypanosoma cruzi, chagas disease, b cell, cd4+ t cells, inflammation

                Comments

                Comment on this article