Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

<p>Abstract</p> <p>Background</p> <p>Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with <it>P. aeruginosa </it>by a Th17-mediated mechanism.</p> <p>Results</p> <p>Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the <it>P. aeruginosa </it>strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against <it>P. aeruginosa </it>in vitro.</p> <p>Conclusions</p> <p>Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with <it>P. aeruginosa </it>in the CF lung.</p

Genetic Traces of Recent Long-Distance Dispersal in a Predominantly Self-Recruiting Coral

Understanding of the magnitude and direction of the exchange of individuals among geographically separated subpopulations that comprise a metapopulation (connectivity) can lead to an improved ability to forecast how fast coral reef organisms are likely to recover from disturbance events that cause extensive mortality. Reef corals that brood their larvae internally and release mature larvae are believed to show little exchange of larvae over ecological times scales and are therefore expected to recover extremely slowly from large-scale perturbations.Using analysis of ten DNA microsatellite loci, we show that although Great Barrier Reef (GBR) populations of the brooding coral, Seriatopora hystrix, are mostly self-seeded and some populations are highly isolated, a considerable amount of sexual larvae (up to approximately 4%) has been exchanged among several reefs 10 s to 100 s km apart over the past few generations. Our results further indicate that S. hystrix is capable of producing asexual propagules with similar long-distance dispersal abilities (approximately 1.4% of the sampled colonies had a multilocus genotype that also occurred at another sampling location), which may aid in recovery from environmental disturbances.Patterns of connectivity in this and probably other GBR corals are complex and need to be resolved in greater detail through genetic characterisation of different cohorts and linkage of genetic data with fine-scale hydrodynamic models

Coral thermal tolerance shaped by local adaptation of photosymbionts

Coral thermal tolerance is strongly influenced by the identity of obligate photosymbionts, which encompass numerous types belonging to the dinoflagellate genus. Symbiodinium(1). Physiological advantages achieved by partnering with functionally diverse symbionts(2-4) have been assumed to be available only to corals that can form associations with multiple Symbiodinium types. Functional variation among populations of the same type of Symbiodinium has been overlooked, despite local adaptation being feasible because of large population sizes(5,6), genetic isolation(7,8) and short asexual generation times(9). Here we demonstrate divergent thermal tolerance in a generalist Symbiodinium type from two different thermal environments. Symbiodinium from the warmer reef maintained greater photochemical performance and survivorship when exposed to an elevated temperature of 32 °C, both in symbiosis and in culture. Juvenile corals associated with Symbiodinium from the warmer reef grew rapidly when exposed to 32 °C, yet underwent bleaching and tissue death when associated with Symbiodinium from the cooler reef. These results demonstrate that Symbiodinium types can adapt to local differences in thermal climate and that this adaptation shapes the fitness of coral hosts. If Symbiodinium populations are able to further adapt to increases in temperature at the pace at which ocean climates warm, they may assist corals to increase their thermal tolerance and persist into the future