Central nervous system commitment in Chagas disease.

The involvement of the central nervous system (CNS) during human acute and chronic Chagas disease (CD) has been largely reported. Meningoencephalitis is a frequent finding during the acute infection, while during chronic phase the CNS involvement is often accompanied by behavioral and cognitive impairments. In the same vein, several studies have shown that rodents infected with Trypanosoma cruzi (T. cruzi) display behavior abnormalities, accompanied by brain inflammation, in situ production of pro-inflammatory cytokines and parasitism in diverse cerebral areas, with involvement of microglia, macrophages, astrocytes, and neurons. However, the mechanisms used by the parasite to reach the brain remain now largely unknown. Herein we discuss the evidence unravelling the CNS involvement and complexity of neuroimmune interactions that take place in acute and chronic CD. Also, we provide some clues to hypothesize brain infections routes in human and experimental acute CD following oral infection by T. cruzi, an infection route that became a major CD related public health issue in Brazil.

Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations.

BACKGROUND: Etiologic studies provide evidence that IL-4R and IL-6R receptors may play important roles in the regulatory mechanisms of the development of clinical dengue, especially in children which is a segment of the population with high severe dengue risk. Moreover, the allele frequencies and genetic associations may be influenced by the populational genetic background. Therefore, we performed a case-control study to evaluate possible associations between SNPs in IL4R and IL6R genes and clinical dengue in children from two Colombian populations. METHODS: We genotyped the rs1805016 (IL4R) and rs8192284 (IL6R) by PCR-RFLP method, in 298 symptomatic children and 648 asymptomatic controls. Three individual genetic ancestral proportions (APs) (European, Amerindian, African) were inferred by genotyping 29 AIMs (Ancestry informative markers). The variables gender, APs, and the population of origin were used like confusion variables. RESULTS: We found IL4R-rs1805016 GG genotype and G-allele carriers and IL6R-rs8192284 AA genotype associated with clinical dengue in the pooled and Huila samples. Nevertheless, we found no association of these polymorphisms in the sample of Antioquia. CONCLUSIONS: For the first time, we report SNPs in IL4R and IL6R genes associated with clinical dengue, which contributes to understanding the genetic susceptibility to dengue disease. Moreover, these results may be influenced by genetic background and must be evaluated through functional analysis.

Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia.

Functional immunological evidence supports the impact that the host genetic variability has on the susceptibility to develop asymptomatic or symptomatic dengue infection. Children are more prone to develop severe dengue. Thus, we have evaluated possible associations between single-nucleotide polymorphisms (SNPs) located in immune genes and the development of symptomatic dengue in children from two Colombian populations with differences in genetic backgrounds and geographical features. We genotyped 15 SNPs (in 12 genes) in 298 symptomatic children and 648 healthy controls. Ancestry proportions (APs) were inferred by genotyping 29 ancestry informative markers. We observed four SNPs associated with susceptibility to develop dengue in NOD1, RIPK2, MICB, or PLCE1 genes. Conversely, we found one SNP in TNF gene and two haplotypes in the IKBKE gene associated with resistance to develop dengue. These associations were adjusted by gender, APs, and the population of origin because the association of polymorphisms may be different in admixed populations like Colombian. To our knowledge, this is the first reported association study with dengue in IKBKE, RIPK2, and NOD1 genes. We have also confirmed previously reported associations in MICB and PLCE1 genes with dengue. Overall, our results contribute to the understanding of the genetic susceptibility/resistance to develop symptomatic dengue. Nevertheless, these associations must be validated through functional analysis.