Resolvin D2 induces anti-microbial mechanisms in a model of infectious peritonitis and secondary lung infection.

In severe bacterial infections, there is a pro-inflammatory response to promote bacterial clearance but this response can cause tissue injury. Later, the immune system becomes dysregulated and the host is unable to clear a secondary or a pre-existing infection. Specialized Pro-resolving Mediators (SPMs) such as resolvin D2 (RvD2) have been shown to be beneficial for inflammation/infection resolution in animal models of sepsis but in vivo mechanisms by which RvD2 may promote bacterial clearance and/or attenuate deleterious effects of a secondary infection have not been fully established. In this study, we used the 2-hit model of cecal ligation and puncture (CLP) induced infectious peritonitis and secondary lung infection with Pseudomonas aeruginosa to find possible antimicrobial and immunomodulatory mechanisms of RvD2. We show that RvD2 given as late as 48h after CLP surgery reduced blood bacterial load without altering plasma cytokines compared to mice given saline vehicle. RvD2 increased splenic neutrophil accumulation as well as average reactive oxygen species (ROS) production. There was also an increase in an immature leukocyte population the myeloid derived suppressor cells (MDSCs) in the spleen of RvD2 treated mice. RvD2 reduced lung lavage bacterial load 24h after P. aeruginosa administration and significantly decreased lung lavage levels of IL-23, a cytokine essential in the Th-17 inflammatory response. In addition, we show that RvD2 increased the number of non-inflammatory alveolar macrophages after P. aeruginosa administration compared to saline treated mice. The study uncovered an antimicrobial mechanism of RvD2 where RvD2 increases mature neutrophil and MDSC accumulation into the spleen to promote blood bacterial clearance. The study showed that in this 2-hit model, RvD2 promotes lung bacterial clearance, increased non-inflammatory alveolar macrophage number and inhibits an adaptive immune pathway providing evidence of its resolution mechanism in secondary pulmonary infection.

Different Concentrations of Lactobacillus acidophilus Cell Free Filtrate Have Differing Anti-Biofilm and Immunomodulatory Effects.

Probiotics such as various strains of Lactobacillaceae have been shown to have antimicrobial and immunomodulatory activity. In vitro studies have shown that Lactobacilli can decrease bacterial biofilm formation. Effects on immune cells have been unclear with most studies showing anti-inflammatory activity. The mechanism of effects has not been clearly elucidated. In these studies, we used different concentrations of live Lactobacillus acidophilus as well as cell free filtrate (CFF) derived from different concentrations of bacteria. Use of CFF is advantageous as a therapeutic because in vivo it can directly contact immune cells and its concentration is fixed. Both live cells and CFF inhibited Pseudomonas aeruginosa biofilm formation. Importantly, we show that high concentration CFF destroyed mature biofilm. This activity was not due to a lowered pH per se, as pH matched HCl did not remove mature biofilm. High concentration CFF totally inhibited P. aeruginosa growth and was bactericidal (>99.99%), but low concentration CFF was not bactericidal. To examine the immunomodulatory effects of L. acidophilus, we incubated THP-1 monocytes and derived macrophages with CFF and measured TNFα production. CFF did not significantly increase TNFα production in THP-1 monocytes. When cells were prestimulated with LPS, high concentration CFF increased TNFα production even further. In macrophages, high concentration CFF alone increased TNFα production but did not affect LPS prestimulated cells. In contrast, low concentration CFF decreased TNFα production in LPS prestimulated cells. To elucidate the possible mechanisms for these effects, we repeated the experiments using a NF-κB reporter THP-1 cell line. High concentration CFF increased NF-κB activity in monocytes and macrophages. In LPS prestimulated macrophages, only low concentration CFF reduced NF-κB activity. These results suggest that high concentration CFF alone induced NF-κB expression which could account partially for an increase in TNFα production. On the other hand, in macrophages, the lower non-bactericidal concentration of CFF reduced NF-κB expression and decreased TNFα production after LPS prestimulation. Taken together, the results provide evidence that different concentrations of L. acidophilus CFF possess varying bactericidal, anti-biofilm and immunomodulatory effects. This is important in vivo to evaluate the possible use of L. acidophilus CFF in different conditions.

Socialization of coping with community violence: influences of caregiver coaching, modeling, and family context.

A socialization model of coping with community violence was tested in 101 African American adolescents (55% male, ages 9-13) and their maternal caregivers living in high-violence areas of a mid-sized, southeastern city. Participants completed interviews assessing caregiver coping, family context, and child adjustment. Caregiver-child dyads also discussed a film clip depicting community violence. Parental coaching (caregivers' strategies suggesting how to cope) and child-reported coping were coded from the discussion. Coaching, modeling (caregivers' own coping), and family context each contributed to children's coping with violence. Children's problem-focused coping in response to violence had the strongest associations with changes in their adjustment 6 months later. Implications for interventions with youth and families are discussed.

Violence exposure and adjustment in inner-city youth: child and caregiver emotion regulation skill, caregiver-child relationship quality, and neighborhood cohesion as protective factor.

This short-term, longitudinal interview study used an ecological framework to explore protective factors within the child, the caregiver, the caregiver-child relationship, and the community that might moderate relations between community violence exposure and subsequent internalizing and externalizing adjustment problems and the different patterns of protection they might confer. Participants included 101 pairs of African American female caregivers and one of their children (56% male, M = 11.15 yrs, SD = 1.28) living in high-violence areas of a mid-sized southeastern city. Child emotion regulation skill, felt acceptance from caregiver, observed quality of caregiver-child interaction, and caregiver regulation of emotion each were protective, but the pattern of protection differed across level of the child's ecology and form of adjustment. Implications for prevention are discussed.