Tuberculosis remains a serious threat worldwide. For this reason, it is necessary to identify agents that shorten the duration of treatment, strengthen the host immune system, and/or decrease the damage caused by the infection. Statins are drugs that reduce plasma cholesterol levels and have immunomodulatory, anti-inflammatory and antimicrobial effects. Although there is evidence that statins may contribute to the containment of Mycobacterium tuberculosis infection, their effects on peripheral blood mononuclear cells (PBMCs) involved in the immune response have not been previously described. Using PBMCs from 10 healthy subjects infected with M. tuberculosis H37Rv, we analyzed the effects of simvastatin on the treatment of the infections in an in vitro experimental model. Direct quantification of M. tuberculosis growth (in CFU/mL) was performed. Phenotypes and cell activation were assessed via multi-color flow cytometry. Culture supernatant cytokine levels were determined via cytokine bead arrays. The induction of apoptosis and autophagy was evaluated via flow cytometry and confocal microscopy. Simvastatin decreased the growth of M. tuberculosis in PBMCs, increased the proportion of NKT cells in culture, increased the expression of co-stimulatory molecules in monocytes, promoted the secretion of the cytokines IL-1β and IL-12p70, and activated apoptosis and autophagy in monocytes, resulting in a significant reduction in bacterial load. We also observed an increase in IL-10 production. We did not observe any direct antimycobacterial activity. This study provides new insight into the mechanism through which simvastatin reduces the mycobacterial load in infected PBMCs. These results demonstrate that simvastatin activates several immune mechanisms that favor the containment of M. tuberculosis infection, providing relevant evidence to consider statins as candidates for host-directed therapy. They also suggest that future studies are needed to define the roles of statin-induced anti-inflammatory mechanisms in tuberculosis treatment.

Zika has been associated with a variety of severe neurologic manifestations including meningitis and encephalitis. We hypothesized that it may also cause mild to subclinical neurocognitive alterations during acute infection or over the long term. In this observational cohort study, we explored whether Zika cause subclinical or mild neurocognitive alterations, estimate its frequency and duration, and compare it to other acute illnesses in a cohort of people with suspected Zika infection, in the region of Tapachula in Chiapas, Mexico during 2016–2018. We enrolled patients who were at least 12 years old with suspected Zika virus infection and followed them up for 6 months. During each visit participants underwent a complete clinical exam, including a screening test for neurocognitive dysfunction (Montreal Cognitive Assessment score). We enrolled 406 patients [37 with Zika, 73 with dengue and 296 with other acute illnesses of unidentified origin (AIUO)]. We observed a mild and transient impact over cognitive functions in patients with Zika, dengue and with other AIUO. The probability of having an abnormal MoCA score (<26 points) was significantly higher in patients with Zika and AIUO than in those with dengue. Patients with Zika and AIUO had lower memory scores than patients with dengue (Zika vs. Dengue: −0.378, 95% CI−0.678 to −0.078; p = 0.014: Zika vs. AIUO 0.264, 95% CI 0.059, 0.469; p = 0.012). The low memory performance in patients with Zika and AIUO accounts for most of the differences in the overall MoCA score when compared with patients with dengue. Our results show a decrease in cognitive function during acute illness and provides no evidence to support the hypothesis that Zika might cause neurocognitive alterations longer than the period of acute infection or different to other infectious diseases. While effects on memory or perhaps other cognitive functions over the long term are possible, larger studies using more refined tools for neurocognitive functioning assessment are needed to identify these.Trial Registration: NCT02831699.

Tuberculosis is one of the 10 leading causes of death in the world. The current treatment is based on a combination of antimicrobials administered for six months. It is essential to find therapeutic agents with which the treatment time can be shortened and strengthen the host immune response against Mycobacterium tuberculosis. M. tuberculosis needs cholesterol to infect and survive inside the host, but the progression of the infection depends to a large extent on the capacity of the immune response to contain the infection. Statins inhibit the synthesis of cholesterol and have pleiotropic effects on the immune system, which have been associated with better results in the treatment of several infectious diseases. Recently, it has been reported that cells treated with statins are more resistant to M. tuberculosis infection, and they have even been proposed as adjuvants in the treatment of M. tuberculosis infection. The aim of this review is to summarize the immunopathogenesis of tuberculosis and its mechanisms of evasion and to compile the available scientific information on the effect of statins in the treatment of tuberculosis.

Dendritic cells (DC) play an important role in the development and maintenance of immune tolerance. Although the inhibitory receptor ILT4/LILRB2 has been related with the tolerogenic phenotype of DC, the possible role of this receptor in the breakdown of DC tolerogenic function in systemic lupus erythematosus (SLE) has not been elucidated. In this study, we analyzed the expression and function of the inhibitory receptor ILT4 in DC from SLE patients. We found that the percentage of ILT4 positive plasmacytoid DC and myeloid DC is significantly diminished in SLE patients. Interestingly, ligation of ILT4 did not affect the maturation or immunogenic capability of DC in healthy controls. In contrast, in SLE patients we observed an inhibitory effect of ILT4 on the immunogenic capability of DC. ILT4 was shown not to have a crucial role in regulating the maturation and function of DC from healthy controls but is partially involved in the maturation process and immunogenic capability of DC from SLE patients, suggesting that other inhibitory receptors, involved in the regulation of DC tolerogenic function, may be impaired in this autoimmune disease.

Background Our purpose was to provide a detailed clinical description, of symptoms and laboratory abnormalities, and temporality in patients with confirmed Zika and dengue infections, and other acute illnesses of unidentified origin (AIUO). Methods/ Principal findings This was a two-year, multicenter, observational, prospective, cohort study. We collected data from patients meeting the Pan American Health Organization’s modified case-definition criteria for probable Zika infection. We identified Zika, dengue chikungunya by RT-PCR in serum and urine. We compared characteristics between patients with confirmed Zika and dengue infections, Zika and AIUO, and Dengue and AIUO at baseline, Days 3,7,28 and 180 of follow-up. Most episodes (67%) consistent with the PAHO definition of probable Zika could not be confirmed as due to any flavivirus and classified as Acute Illnesses of Unidentified Origin (AIUO). Infections by Zika and dengue accounted for 8.4% and 16% of episodes. Dengue patients presented with fever, generalized non-macular rash, arthralgia, and petechiae more frequently than patients with Zika during the first 10 days of symptoms. Dengue patients presented with more laboratory abnormalities (lower neutrophils, lymphocytosis, thrombocytopenia and abnormal liver function tests), with thrombocytopenia lasting for 28 days. Zika patients had conjunctivitis, photophobia and localized macular rash more frequently than others. Few differences persisted longer than 10 days after symptoms initiation: conjunctivitis in Zika infections, and self-reported rash and petechia in dengue infections. Conclusions Our study helps characterize the variety and duration of clinical features in patients with Zika, dengue and AIUO. The lack of diagnosis in most patients points to need for better diagnostics to assist clinicians in making specific etiologic diagnoses.

Dendritic cells (DCs) and regulatory T cells (Tregs) play an essential role in myocarditis. However, a particular DC phenotype in this disease has not been assessed. Herein, we aim to evaluate myeloid (mDCs) and plasmacytoid DC (pDC) phenotype, as well as Treg levels from myocarditis patients and healthy controls. Using multiparametric flow cytometry, we evaluated the levels of myeloid DCs (mDCs), plasmacytoid DCs (pDCs), and Tregs in peripheral blood from myocarditis patients ( n = 16 ) and healthy volunteers ( n = 16 ) and performed correlation analysis with clinical parameters through Sperman test. DCs from myocarditis patients showed a higher expression of costimulatory molecules while a diminished expression of the inhibitory receptors, ILT2 and ILT4. Even more, Treg cells from myocarditis patients displayed higher levels of FOXP3 compared to controls. Clinically, the increased levels of mDCs and their higher expression of costimulatory molecules correlate with a worse myocardial function, higher levels of acute phase reactants, and higher cardiac enzymes. This study shows an activating phenotype of circulating DCs from myocarditis patients. This proinflammatory status may contribute to the pathogenesis and immune deregulation in acute myocarditis.

The lack of efficient and cost-effective diagnostic tools contributes to poor control of tuberculosis in endemic countries. Moreover, host biological processes influence susceptibility, and infection resolution. It is well known that comorbidities such as type 2 diabetes mellitus (DM2) affect the host immune response, making individuals more susceptible to Mycobacterium tuberculosis infection. Currently, there are no laboratory tools that can identify those subjects who have a higher risk of developing the disease. In this study, we used a whole blood mycobacterial growth inhibition assay to assess the immune response capacity to inhibit mycobacterial growth between healthy subjects and those living with DM2 with optimal and poor glycemic control. We also measured cytokine levels in the culture supernatant by cytokine bead arrays. We included 89 patients with DM2: 54 patients with optimal control (mean age 56.2 ± 11.75 years) and 35 patients with poor control (mean age 52.05 ± 9.94 years). We also included 44 healthy subjects as controls (mean age 42.12 ± 11.75 years). We compared the Δlog UFC (a value that represents the difference between mycobacterial growth in the control tube versus the subject’s blood) between each group. Our results demonstrate that patients with DM2 had a lower capacity to inhibit M. tuberculosis growth (Δlog UFC DM2 subjects 0.9581 (-0.3897 to 2.495) vs Δlog UFC healthy subjects 0.7190 (-0.2678 to 2.098); p=0.013). Comparing subjects living with DM2 (optimal and poor glycemic control) vs healthy subjects, we found only significant differences between healthy subjects and patients poorly controlled (Δlog UFC optimal control group 0.876 (-0.3897 to 2.495); Δlog UFC poor control group 1.078 (0.068 to 2.33); Δlog UFC healthy subjects 0.7190 (-0.2678 to 2.098); p= 0.022). Therefore, glycemic control assessed by glycosylated hemoglobin values influences the capacity of the host to control the infection. Our results confirm that the whole blood mycobacterial growth inhibition assay has potential utility as an in vitro marker of M. tuberculosis immunological control in vivo in subjects living with DM2. This assay can be used to evaluate the immune response of each individual against M. tuberculosis, allowing clinicians to choose a more specific host-directed therapy.

Background Human Rhinoviruses (HRV) are a common cause of influenza-like illness, with the ability to infect the upper and lower respiratory tracts. In this study we aim to describe the clinical and molecular features of HRV infection in Mexican children and adults. Methods We performed a hospital-based, 4-year multicenter prospective observational cohort study of patients with influenza-like illness. Participants that tested positive for HRV were included. We described demographic, clinical, and laboratory characteristics, and the association between rhinovirus types, illness severity, and clinical outcomes. Results Of the 5662 subjects recruited, 1473 (26%) had HRV; of those, 988 (67.1%) were adults (≥18) and 485 (32.9%) were children. 167 (11.33%) samples were sequenced; 101 (60.5%) were rhinovirus type A (HRV-A), 22 (13.2%) were rhinovirus type B (HRV-B), and 44 (26.3%) were rhinovirus type C (HRV-C). 30.5% of children and 23.5% of adults were hospitalized (non-ICU). The odds of HRV-C are higher than HRV-A for participants in the ICU (compared to outpatient), and when platelets, lymphocytes, WBC, and LDH are increased. The odds of HRV-C are higher than HRV-A and HRV-B with shortness of breath. The odds of HRV-A are higher than HRV-B, and the odds of HRV-B are higher than HRV-C, when mild symptoms like muscle ache and headache occur. Conclusions Rhinoviruses are a common cause of influenza-like illness. It is necessary to improve the surveillance, testing, and species identification for these viruses to understand different clinical presentations and risk factors associated with worse outcomes.