The NLRP3 inflammasome is involved with the pathogenesis of Mayaro virus.

Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3-/-, Aim2-/-, Asc-/-and Casp1/11-/-mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1ß. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1ß and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans.

Effects of non-surgical periodontal therapy on clinical and immunological profile and oral colonization of Candida spp in HIV-infected patients with chronic periodontitis.

BACKGROUND: After the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has become a chronic controllable disease. For this reason, chronic conditions related to both HIV infection and senescence, such as chronic periodontitis (CP) need to be studied. This study investigated the impact of non-surgical periodontal therapy (NSPT) on clinical and immunological features of CP, and on oral colonization by Candida spp. in HIV-infected and non-HIV-infected individuals. METHODS: HIV-infected (test group) and non-HIV-infected (control group) adults patients with CP were selected. Gingival bleeding index (GI), probing depth (PD), clinical attachment level (CAL), number of teeth, CD4+ T lymphocytes and viral load (only for HIV-infected individuals), salivary cytokines (interleukin, [IL]-6, IL-8, and tumoral necrosis factor-alpha [TNF-α]), and oral Candida infection (colony forming units and species) were assessed at baseline, and 30 and 90 days after NSPT. RESULTS: Twenty-two HIV-infected patients and 20 non-HIV-infected patients were evaluated. Candida counts and salivary IL-6, IL-8, and TNF-a levels were higher in the test group than in the control group. Both groups showed a decrease in oral Candida counts, GI, PD, IL-6, and IL-8 as well as gain in CAL at 30 and 90 days after NSPT. In addition, patients in the test group showed an increase of CD4+ T lymphocytes and a decrease of viral load. CONCLUSION: NSPT had a beneficial impact on clinical and immunological parameters of CP, reduction of oral Candida counts, and improvement of HIV-infection status.

Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 α-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

Combined use of the polymerase chain reaction and detection of adenosine deaminase activity on pleural fluid improves the rate of diagnosis of pleural tuberculosis.

STUDY OBJECTIVES: Evaluation of the combined use of polymerase chain reaction (PCR) and adenosine deaminase (ADA) activity on the diagnosis of pleural tuberculosis (pTB) in a region of high prevalence of tuberculosis. PATIENTS: PCR and determination of ADA activity were performed on the pleural fluid of every patient presenting with pleural effusion suspected to be associated with tuberculosis. The case definition of pTB involved parameters including the combination of clinical and radiologic findings; biochemical, microbiologic, and cytologic examination of the pleural fluid; and the histopathologic findings of pleural fragments obtained by biopsy. The diagnosis of pTB was confirmed in any patient presenting with positive culture findings of Mycobacterium tuberculosis, either on the pleural fluid or other biological material, or the presence of histopathologic findings suggestive of pTB on pleural biopsy, and also, in the absence of negative laboratory results, those patients with clinical improvement after empirical treatment. RESULTS: We studied 45 patients with pleural effusion. Of these, 16 patients met the diagnosis of pTB by our broad case definition. PCR findings were positive in six patients. The reaction was also positive in a patient whose diagnosis of tuberculosis could not be confirmed. ADA activity was considered positive in 11 patients with pTB. The combined use of PCR and ADA activity confirmed pTB in 14 patients; however, when analyzed in combination with the conventional methods, diagnosis of pTB was achieved in all 16 patients. CONCLUSION: Our results show that, even in a highly endemic area, neither PCR nor ADA activity should be relied on as a single test that substitutes for the diagnostic methods already available, but rather they should be used as an extra tool in the diagnosis of pTB. The combined analysis of PCR and ADA activity, however, is a very useful diagnostic approach to achieve a more rapid and precise diagnosis in the cases of pTB.