Attempted Passive Prophylaxis with a Monoclonal Anti-Burkholderia Pseudomallei Exopolysaccharide Antibody in a Murine Model of Melioidosis

Melioidosis is a severe gram-negative infection caused by the facultative intracellular bacterium Burkholderia pseudomallei, which is responsible for a broad spectrum of symptoms in both humans and animals. No licensed vaccine currently exists. This study evaluated the protective effect of a monoclonal antibody (Mab Ps6F6) specific to B. pseudomallei exopolysaccharide in an outbred murine model of sub-acute melioidosis. When administered before the infectious challenge, Ps6F6 significantly increased resistance to infection and restrained bacterial burden in the spleen over a 30-days period. Patterns of IFN-γ production were similar in the treated and non treated groups of mice. However, Ps6F6 lowered IFN-γ levels over the duration of the assay period, except on day 1, suggesting a transient and rapid production of IFN-γ under Ps6F6 control. Minor but persisting increases occurred in IL-12 levels while TNF-α was detected only in the controls at the later stages of infection. No IL-10 secretion was detected in both groups of mice. These data suggest that passive prophylaxis with Mab Ps6F6 provide a moderate and transient induction of inflammatory responses in infected mice but failed to trigger a sterilizing protective immunity.     

Intensity and frequency of physical activity and high blood pressure in adolescents: A longitudinal study

Despite limited evidence on the association between physical activity (PA) and blood pressure (BP) in youth, experts recommend that adolescents engage regularly in moderate‐to‐vigorous PA. We examined the relationships between PA intensity and frequency and the likelihood of having high BP in a population‐based cohort of adolescents from Montréal, Canada. PA was self‐reported every 3 months from grade 7 to 11, and BP was measured at ages 12.8, 15.2, and 17.0 years on average. We analyzed data from 993 participants (mean [SD] age = 16.0 [1.0], 51.6% female) with BP data at ages 15.2 and/or 17.0 years, using pooled ordinal logistic regression. BP (normal/elevated/hypertensive range) was the outcome, and past‐year PA intensity and frequency were potential predictors. Eight percent of participants had elevated BP (120‐129/<80), and 3.2% had BP in the hypertensive range (≥130/≥80). Participants engaged in a median (interquartile range) of 7.0 (4.5, 9.3) and 5.5 (2, 10.8) moderate and vigorous PA sessions/week, respectively. After adjusting for age, sex, mother's education, use of alcohol and cigarette consumption, engaging in PA more intense than light during the previous year was associated with a lower odds of having BP in the hypertensive range (ORs [95% CIs] = 0.93 [0.88, 0.97] to 0.97 [0.94, 0.99]). The relationships were not altered by adjusting for BMI. Our findings support recommendations that adolescents engage in at least moderate PA on a regular basis to prevent development of BP in the hypertensive range.     

Cell crawling mediates collective cell migration to close undamaged epithelial gaps

Fundamental biological processes such as morphogenesis and wound healing involve the closure of epithelial gaps. Epithelial gap closure is commonly attributed either to the purse-string contraction of an intercellular actomyosin cable or to active cell migration, but the relative contribution of these two mechanisms remains unknown. Here we present a model experiment to systematically study epithelial closure in the absence of cell injury. We developed a pillar stencil approach to create well-defined gaps in terms of size and shape within an epithelial cell monolayer. Upon pillar removal, cells actively respond to the newly accessible free space by extending lamellipodia and migrating into the gap. The decrease of gap area over time is strikingly linear and shows two different regimes depending on the size of the gap. In large gaps, closure is dominated by lamellipodium-mediated cell migration. By contrast, closure of gaps smaller than 20 μm was affected by cell density and progressed independently of Rac, myosin light chain kinase, and Rho kinase, suggesting a passive physical mechanism. By changing the shape of the gap, we observed that low-curvature areas favored the appearance of lamellipodia, promoting faster closure. Altogether, our results reveal that the closure of epithelial gaps in the absence of cell injury is governed by the collective migration of cells through the activation of lamellipodium protrusion.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.