Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults. CVID patients often present changes in the frequency and function of B lymphocytes, reduced number of Treg cells, chronic immune activation, recurrent infections, high incidence of autoimmunity and increased risk for malignancies. We hypothesized that the frequency of B10 cells would be diminished in CVID patients because these cells play an important role in the development of Treg cells and in the control of T cell activation and autoimmunity. Therefore, we evaluated the frequency of B10 cells in CVID patients and correlated it with different clinical and immunological characteristics of this disease. Forty-two CVID patients and 17 healthy controls were recruited for this study. Cryopreserved PBMCs were used for analysis of T cell activation, frequency of Treg cells and characterization of B10 cells by flow cytometry. IL-10 production by sorted B cells culture and plasma sCD14 were determined by ELISA. We found that CVID patients presented decreased frequency of IL-10-producing CD24hiCD38hi B cells in different cell culture conditions and decreased frequency of IL-10-producing CD24hiCD27+ B cells stimulated with CpG+PIB. Moreover, we found that CVID patients presented lower secretion of IL-10 by sorting-purified B cells when compared to healthy controls. The frequency of B10 cells had no correlation with autoimmunity, immune activation and Treg cells in CVID patients. This work suggests that CVID patients have a compromised regulatory B cell compartment which is not correlated with clinical and immunological characteristics presented by these individuals.

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Common variable immunodeficiency (CVID) is characterized by low levels of Igs leading to increased risk of infections. Mucosal-associated invariant T (MAIT) cells are a recently identified population of innate T cells with potent antibacterial activity. We hypothesized that CVID is associated with alterations in MAIT cells. Cryopreserved PBMC from CVID patients and healthy controls were used to study the frequency, phenotype, and response to Escherichia coli stimulation of MAIT cells by flow cytometry. MAIT cell frequency and absolute counts were depressed in CVID. Residual MAIT presented elevated coexpression of CD38 and HLA-DR, and reduced expression of CCR6, whereas levels of CD127 (IL-7 receptor) were unchanged. CVID patients also had an accumulation of MAIT cells lacking the critical transcription factors eomesodermin and promyelocytic leukemia zinc finger protein. MAIT cell frequency was inversely associated with levels of soluble CD14, with coexpression of CD38 and HLA-DR, and accumulation of MAIT cells lacking eomesodermin or promyelocytic leukemia zinc finger protein expression. None of these changes were normalized by IgG replacement therapy. Finally, MAIT cells from CVID patients displayed poor IFN-γ responses to E. coli stimulation, in part due to defective Ag presentation, and these responses were increased by pretreatment with IL-7. Defective MAIT cell response may contribute to the increased incidence of microbial infections seen in CVID patients on IgG replacement therapy.

As infecções por cepas de Staphylococcus aureus crescem a cada ano em indivíduos soropositivos, fato esse que pode indicar internações recentes e amplo uso de antibióticos, e são apontadas como responsáveis pela morbimortalidade desses pacientes. O presente estudo teve como objetivo avaliar a prevalência de colonização por S. aureus na cavidade nasal de pacientes portadores de HIV acompanhados pela Seção Centro de Referência em AIDS de Santos/SP (SECRAIDS - Santos) e qualificar o perfil de resistência aos antimicrobianos das cepas isoladas. Foram avaliados nesse estudo 21 pacientes portadores de HIV. Questionários estruturados foram aplicados aos pacientes soropositivos para determinar sua rotina em ambientes ambulatoriais e histórico de doenças e internações. O isolamento e identificação das cepas de S. aureus foi realizado por semeadura de superfície em ágar seletivo. Testes bioquímicos foram realizados para corroboração dos resultados previstos. As cepas de Staphylococcus spp. isoladas e identificadas foram submetidas ao Teste de Sensibilidade aos Antimicrobianos (TSA) por disco-difusão. Foi possível avaliar que 90% dos pacientes soropositivos apresentaram colonização por Staphylococcus spp., dos quais 47,6% corresponderam a cepas de S. aureus. Dentre as amostras isoladas, 20% foram classificadas como MRSA (Staphylococcus aureus Resistente à Meticilina). Resultados semelhantes aos dados descritos na literatura corroboram com a alta prevalência de colonização por S. aureus e cepas MRSA em pacientes soropositivos. A investigação por MRSA torna-se cada vez mais importante, tanto para melhorar a qualidade de vida do paciente em tratamento, quanto para prevenir e erradicar o carreamento dessas bactérias oportunistas.