Maternal Th17 Profile after Zika Virus Infection Is Involved in Congenital Zika Syndrome Development in Children.

Brazil is one of the countries that experienced an epidemic of microcephaly and other congenital manifestations related to maternal Zika virus infection which can result in Congenital Zika Syndrome (CZS). Since the Zika virus can modulate the immune system, studying mothers' and children's immune profiles become essential to better understanding CZS development. Therefore, we investigated the lymphocyte population profile of children who developed CZS and their mothers' immune response in this study. The study groups were formed from the Plaque Reduction Neutralization Test (PRNT) (CZS+ group) result. To evaluate the lymphocyte population profile, we performed phenotyping of peripheral lymphocytes and quantification of serum cytokine levels. The immunophenotyping and cytokine profile was correlated between CSZ+ children and their mothers. Both groups exhibited increased interleukin-17 levels and a reduction in the subpopulation of CD4+ T lymphocytes. In contrast, the maternal group showed a reduction in the population of B lymphocytes. Thus, the development of CZS is related to the presence of an inflammatory immune profile in children and their mothers characterized by Th17 activation.

Maternal Immune Response to ZIKV Triggers High-Inflammatory Profile in Congenital Zika Syndrome.

The immunological mechanisms involved in the development of congenital Zika syndrome (CZS) have yet to be fully clarified. This study aims to assess the immuno-inflammatory profile of mothers and their children who have been diagnosed with CZS. Blood samples, which were confirmed clinically using the plaque reduction neutralization test (PRNT), were collected from children with CZS and their mothers (CZS+ group). Samples were also collected from children who did not develop CZS and had a negative PRNT result and from their mothers (CZS- group). The data demonstrated a correlation between the leukocyte profile of CZS+ children and their mothers, more evident in monocytes. Monocytes from mothers of CZS+ children showed low expression of HLA and elevated hydrogen peroxide production. CZS+ children presented standard HLA expression and a higher hydrogen peroxide concentration than CZS- children. Monocyte superoxide dismutase activity remained functional. Moreover, when assessing the monocyte polarization, it was observed that there was no difference in nitrite concentrations; however, there was a decrease in arginase activity in CZS+ children. These data suggest that ZIKV infection induces a maternal immuno-inflammatory background related to the child's inflammatory response after birth, possibly affecting the development and progression of congenital Zika syndrome.

Tityus serrulatus scorpion venom improves survival and lung inflammation in lethal sepsis induced by CLP in mice.

Tityus serrulatus venom (Tsv) modifies the behavior of immune cells and induces the production of inflammatory and anti-inflammatory cytokines; such action may interfere with physiological or pathological states. Because sepsis is characterized as an inflammatory disorder, the aim of present study was to investigate the effect of a non-lethal dose of Tsv in mice submitted to a polymicrobial infection by cecal ligation and puncture (CLP) model. The parameters evaluated were survival index, cellularity on lymphoid organs, peritoneal cavity and brochoalveolar space, production of IL-10, IL-12, IL-6, TNF-α, IFN-γ and MCP-1, pulmonary inflammation and oxidative burst. The results demonstrated that in sharp contrast to CLP group in which sepsis was lethal in a 24 h period all mice pretreated with Tsv survived even 60 h after CLP. Lung inflammation, another hallmark of CLP group, was also dramatically down regulated in Tsv/CLP group. Despite pretreatment with Tsv did not reduce the inflammatory serum cytokines when compared to CLP group; there was an increase in IL-10. In conclusion, subcutaneous Tsv administration 6 h before CLP was able to control the harmful effects of sepsis (lethality and lung inflammation). We suggest that both systemic IL-10 and oxidative burst are involved in this effect.

Immune cells recruitment and activation by Tityus serrulatus scorpion venom.

Despite several studies showed that the Tityus serrulatus scorpion venom (Tsv) induces an inflammatory response, just a few have investigated the effect of the venom on the immune response. Therefore, the aim of this study was to evaluate alterations of venom application on lymphoid organs and on the recruitment and activation of cells and also on the cytokine production. Swiss male mice (2-3 months, 20-25 g) received a non-lethal dose of crude Tsv (200 µg/kg), diluted in sterile PBS by subcutaneous route. Control animals received only sterile PBS. The animals were sacrificed after 30, 120 and 360 min. The inflammatory parameters studied were skin histology at the site of venom application, leukocyte count, and blood cytokine levels (IL-6, IL-10, and TNF-α). Inguinal lymph node, spleen and bone marrow cellularity was determined for evaluation of the Tsv effect on immune system organs. The results showed that Tsv caused no local inflammation, but it induced an increase of blood neutrophils and serum IL-6, TNF-α and IL-10. After 360 min of envenomation there was a reduction in the cells number from peritoneum and spleen, but there was an increase in the cell number from lymph nodes. In conclusion, the Tsv induces systemic alterations characterized by changes in the cell number in lymphoid organs, increase pro and anti-inflammatory cytokines.