Jeffrey Yu

The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19(-/-)) and IL-17R-deficient (IL-17RA(-/-)) mice experienced severe OPC, whereas Th1-deficient (IL-12p35(-/-)) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19(-/-) and IL-17RA(-/-), but not IL-12(-/-), mice, and TCR-alphabeta cells were more important than TCR-gammadelta cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and beta defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.

IL-17 and its receptor are founding members of a novel family of inflammatory cytokines. IL-17 plays a pathogenic role in rheumatoid arthritis (RA)-associated bone destruction. However, IL-17 is also an important regulator of host defense through granulopoiesis and neutrophil trafficking. Therefore, the role of IL-17 in pathogen-initiated bone loss was not obvious. The most common form of infection-induced bone destruction occurs in periodontal disease (PD). In addition to causing significant morbidity, PD is a risk factor for atherosclerotic heart disease and chronic obstructive pulmonary disease (COPD). Similar to RA, bone destruction in PD is caused by the immune response. However, neutrophils provide critical antimicrobial defense against periodontal organisms. Since IL-17 is bone destructive in RA but a key regulator of neutrophils, we examined its role in inflammatory bone loss induced by the oral pathogen Porphyromonas gingivalis in IL-17RA-deficient mice. These mice showed enhanced periodontal bone destruction, suggesting a bone-protective role for IL-17, reminiscent of a neutrophil deficiency. Although IL-17RA-deficient neutrophils functioned normally ex vivo, IL-17RA knock-out (IL-17RA(KO)) mice exhibited reduced serum chemokine levels and concomitantly reduced neutrophil migration to bone. Consistently, CXCR2(KO) mice were highly susceptible to alveolar bone loss; interestingly, these mice also suggested a role for chemokines in maintaining normal bone homeostasis. These results indicate a nonredundant role for IL-17 in mediating host defense via neutrophil mobilization.

A 65 days feeding trial was conducted to evaluate the potential of black soldier fly larvae (BSFL) as a fish meal (FM) protein alternative in the diet of yellow catfish. Fish meal protein was replaced with BSFL meal protein at 0% (control), 13%, 25%, 37%, 48%, 68%, 85% and 100%. Compared with the control group, increased growth performances (e.g. weight gain rate increased by 21.7%) and immune indexes (e.g. serum lysozyme activity increased by 6.8%) of yellow catfish fed with diets in which a maximum of 48% FM protein was replaced by BSFL meal protein was determined. The diet in which 25% FM protein was replaced by BSFL meal protein resulted in the greatest growth performances (e.g. weight gain rate increased by 29.1%) and immune indexes (e.g. serum lysozyme activity increased by 31.9%) as well as the lowest feed conversion ratio (0.9) among all diets tested. No significant differences in survival rate, body indexes or composition were determined among all treatments. Therefore, BSFL meal protein has the potential to partially replace FM protein in the diet of yellow catfish, and it may also enhance the immunocompetence of the fish.

Previous longitudinal studies have consistently shown an association between attendance at religious services and lower all-cause mortality, but the literature on associations between other measures of religion and spirituality (R/S) and mortality is limited. We followed 36,613 respondents from the Black Women's Health Study from 2005 through December 31, 2013 to assess the associations between R/S and incident all-cause mortality using proportional hazards models. After control for numerous demographic and health covariates, together with other R/S variables, attending religious services several times per week was associated with a substantially lower mortality rate ratio (mortality rate ratio = 0.64, 95% confidence interval: 0.51, 0.80) relative to never attending services. Engaging in prayer several times per day was not associated with mortality after control for demographic and health covariates, but the association trended towards a higher mortality rate ratio when control was made for other R/S variables (for >2 times/day vs. weekly or less, mortality rate ratio = 1.28, 95% confidence interval: 0.99, 1.67; P-trend < 0.01). Religious coping and self-identification as a very religious/spiritual person were associated with lower mortality when adjustment was made only for age, but the association was attenuated when control was made for demographic and health covariates and was almost entirely eliminated when control was made for other R/S variables. The results indicate that service attendance was the strongest R/S predictor of mortality in this cohort.