Liver immunopathogenesis in fatal cases of dengue in children: detection of viral antigen, cytokine profile and inflammatory mediators.

Introduction: Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood. Objective: In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children. Methods: Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns. Results: Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein. Conclusion: Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.

Insights of OxyR role in mechanisms of host-pathogen interaction of Corynebacterium diphtheriae.

Corynebacterium diphtheriae, the leading causing agent of diphtheria, has been increasingly related to invasive diseases, including sepsis, endocarditis, pneumonia, and osteomyelitis. Oxidative stress defense is required not only for successful growth and survival under environmental conditions but also in the regulation of virulence mechanisms of human pathogenic species, by promoting mucosal colonization, survival, dissemination, and defense against the innate immune system. OxyR, functioning as a negative and/or positive transcriptional regulator, has been included among the major bacterial coordinators of antioxidant response. OxyR was first reported as a repressor of catalase expression in C. diphtheriae. However, the involvement of OxyR in C. diphtheriae pathogenesis remains unclear. Accordingly, this work aimed to investigate the role of OxyR in mechanisms of host-pathogen interaction of C. diphtheriae through the disruption of the OxyR of the diphtheria toxin (DT)-producing C. diphtheriae CDC-E8392 strain. The effects of OxyR gene disruption were analyzed through interaction assays with human epithelial cell lines (HEp-2 and pneumocytes A549) and by the induction of experimental infections in Caenorhabditis elegans nematodes and Swiss Webster mice. The OxyR disruption exerted influence on NO production and mechanism accountable for the expression of the aggregative-adherence pattern (AA) expressed by CDC-E8392 strain on human epithelial HEp-2 cells. Moreover, invasive potential and intracytoplasmic survival within HEp-2 cells, as well as the arthritogenic potential in mice, were found affected by the OxyR disruption. In conclusion, data suggest that OxyR is implicated in mechanisms of host-pathogen interaction of C. diphtheriae.