RESUMO
Infection is the leading risk factor of liver transplantation-related death. Aspergillosis is a life-threatening complication in immune-compromised patients, and is the cause of approximately 2/3 of deaths in liver transplant recipients. In our previous studies, we found a regulatory T cell (Treg) population that showed significantly increased immune tolerance in Aspergillus-infected liver transplant recipients. Furthermore, interleukin (IL)-17 production was also increased, and an IL-17-producing Treg cell subset was identified in these patients. Functional studies of the role of these IL-17-producing Treg cells in the induction of immune tolerance are needed to help reduce the death rate of liver transplantation recipients. This study included 75 liver transplant recipients with and without histologically confirmed aspergillosis after liver transplantation. The percentage of T cell population subsets producing cytokines was detected by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay in peripheral blood. Complements in blood serum were also examined. The risk of acute rejection was lower in Aspergillus-infected liver transplant recipients compared to the non-Aspergillus-infected group; the CD4(+)CD25(hi) T cell population in peripheral blood was higher and the CD4(+)CD45RA-CD45RO(+) T cell population was lower. There was no significant difference between the CD4(+)CD25(lo)CD45RA(+) and CD4(+)CD25(lo)CD45RA- T cell populations. Moreover, IL-6 decreased and IL-4 increased in the blood serum of Aspergillus-infected liver transplant recipients. Together, these results indicate that the incidence of graft rejection in liver transplantation recipients with Aspergillus infections was lower than that of the non-infected group, and suggests a mechanism for this effect.
Assuntos
Aspergilose/imunologia , Aspergillus/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Fígado , Subpopulações de Linfócitos T/imunologia , Adulto , Aspergilose/microbiologia , Antígenos CD4/genética , Antígenos CD4/imunologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-4/agonistas , Interleucina-4/biossíntese , Interleucina-4/sangue , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Interleucina-6/sangue , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/imunologia , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/microbiologiaRESUMO
The present paper is an overview of the primary events that are associated with the histoplasmosis immune response in the murine model. Valuable data that have been recorded in the scientific literature have contributed to an improved understanding of the clinical course of this systemic mycosis, which is caused by the dimorphic fungus Histoplasma capsulatum. Data must be analyzed carefully, given that misinterpretation could be generated because most of the available information is based on experimental host-parasite interactions that used inappropriate proceedings, i.e., the non-natural route of infection with the parasitic and virulent fungal yeast-phase, which is not the usual infective phase of the etiological agent of this mycosis. Thus, due to their versatility, complexity, and similarities with humans, several murine models have played a fundamental role in exploring the host-parasite interaction during H. capsulatum infection.
Assuntos
Histoplasma/imunologia , Histoplasmose/imunologia , Imunidade Inata , Imunidade Adaptativa , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/microbiologia , Animais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/microbiologia , Parede Celular/química , Parede Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Modelos Animais de Doenças , Histoplasma/crescimento & desenvolvimento , Histoplasma/patogenicidade , Histoplasmose/microbiologia , Histoplasmose/patologia , Especificidade de Hospedeiro , Humanos , Camundongos , Especificidade da Espécie , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/microbiologiaRESUMO
Evaluation of: Nobrega C, Nunes-Alves C, Cerqueira-Rodrigues B et al. T cells home to the thymus and control infection. J. Immunol. 190, 1646-1658 (2013). It is well documented that the thymus is a target organ for a large variety of pathogens (virus, bacteria, fungi and protozoa). Moreover, the presence of pathogen-derived antigens in the thymus of infected mice seems to interfere with the capacity of mature T cells to respond to the invading organism. In this way, Nobrega and colleagues demonstrated in 2010 that Mycobacterium avium infection in the thymus leads to the appearance of differentiated T cells tolerogenic for bacterial antigens. In the present and elegant study, the same group demonstrates that T-cell recirculation from the periphery to the thymus is a mechanism that allows the immune system to respond to thymic infection. A Mycobacterium-infected thymus increases the production of Th1-effector chemokines, such as CXCL9 and CXCL10, which in turn recruit CXCR3(+) peripheral T cells involved in intrathymic bacterial control. Taken together, these findings may represent an important issue of the host response, in terms of different pathogens able to infect the thymus.
Assuntos
Movimento Celular/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/microbiologia , Timo/imunologia , Timo/microbiologia , AnimaisRESUMO
Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB(4) induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB(4) is also important in early effector T cell recruitment that is mediated by LTB(4) receptor 1, the high-affinity receptor for LTB(4). The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB(4) and IFN-gamma production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase(-/-), a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-beta as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase(-/-)-infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis.
Assuntos
Adjuvantes Imunológicos/fisiologia , Histoplasmose/imunologia , Imunização Secundária , Memória Imunológica , Leucotrieno B4/fisiologia , Subpopulações de Linfócitos T/imunologia , Adjuvantes Imunológicos/antagonistas & inibidores , Adjuvantes Imunológicos/biossíntese , Animais , Antígenos de Fungos/administração & dosagem , Antígenos de Fungos/imunologia , Movimento Celular/imunologia , Citocinas/biossíntese , Vacinas Fúngicas/administração & dosagem , Vacinas Fúngicas/imunologia , Histoplasma/imunologia , Histoplasmose/microbiologia , Histoplasmose/prevenção & controle , Humanos , Imunidade Inata , Leucotrieno B4/antagonistas & inibidores , Leucotrieno B4/biossíntese , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/patologia , Pneumopatias Fúngicas/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/microbiologiaRESUMO
Peripheral blood mononuclear cells from leprosy patients and normal individuals were analysed for their ability to lyse autologous macrophages pulsed with the Mycobacterium leprae 10 kDa heat shock protein (hsp10), an antigen considered to have an important role in the protective responses in leprosy. Strong cytotoxic responses, with an involvement of gammadelta T and class-I and class-II restricted alphabeta T cells and/or CD16+56+ cells, were observed in normal individuals, paucibacillary (PB) and those multibacillary (MB) patients with undetectable bacillary load. On the contrary, only a weak class-II restricted cytotoxic response was observed in those MB patients with positive bacillary load (MB(+)). Simultaneous addition of IFNgamma plus TNFalpha and IL-12 during hsp10 stimulation could partially upregulate the low cytotoxic response observed in MB(+) by enhancing class-II restricted T cell activity and by development of gammadelta T and/or CD16+56+ cell activity. Our results suggest that the ability to mount an effective cytotoxic response against hsp10-pulsed macrophages in leprosy patients is closely related to the patient's bacterial load and not to the clinical form of the disease.