Impact of fascioliasis reinfection on Fasciola hepatica egg shedding: relationship with the immune-regulatory response
ACTA TROPICA
Authors: Adela Valero, M.; Girones, Nuria; Reguera-Gomez, Marta; Perez-Crespo, Ignacio; Pilar Lopez-Garcia, M.; Quesada, Carla; Dolores Bargues, M.; Fresno, Manuel; Mas-Coma, Santiago
Abstract
Fascioliasis is a disease caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm. Control strategies in humans require the use of egg count techniques to calculate the appropriate treatment dose for colic risk prevention. The present study investigates how fascioliasis reinfection affects liver fluke egg shedding and its relationship with the immune-regulatory response. The experimental design reproduced the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 4 weeks (R4), 8 weeks (R8), 12 weeks (R12), and negative control rats. In a longitudinal study (0-20 weeks post-infection, p.i.), serical IgG1 levels and eggs per gram of faeces (epg) were analyzed. In a cross-sectional study, the expression of the genes associated with Th1 (Ifng, Il12a, Il12b, Nos2), Th2 (Il4, Arg1), Treg (Foxp3, Il10, Tgfb, Ebi3), and Th17 (Il17) in the spleen and thymus was analyzed. In R8 and R12, transiently higher averages of epg and epg/worm in reinfected groups vs PI group were detected at least in the weeks following reinfection. The kinetics of IgG1 levels shows that reinfected groups followed a pattern similar to the one in the PI group, but transiently higher averages of IgG1 levels in reinfected groups vs the PI group were detected in the weeks following reinfection. Epg correlated with IgG1 levels and also with systemic Il10 and thymic Ifng, and Il10 expression levels. These results suggest that epg depends on the Th1 and Treg phenotype and that the determination of the fluke burden by epg is likely to be an overestimation in cases of recent reinfection in low burden situations. A strategy to facilitate the implementation of epg count techniques and the subsequent decision on the appropriate treatment dose for each patient to prevent colic risk is required.
Signatures of selection for resistance to Haemonchus contortus in sheep and goats
BMC GENOMICS
Authors: Estrada-Reyes, Zaira M.; Tsukahara, Yoko; Amadeu, Rodrigo R.; Goetsch, Arthur L.; Gipson, Terry A.; Sahlu, Tilahun; Puchala, Richard; Wang, Zaisen; Hart, Steve P.; Mateescu, Raluca G.
Abstract
Background Gastrointestinal nematode infection (GNI) is the most important disease affecting the small ruminant industry in U.S. The environmental conditions in the southern United States are ideal for the survival of the most pathogenic gastrointestinal nematode, Haemonchus contortus. Host genetic variation for resistance to H. contortus allows selective breeding for increased resistance of animals. This selection process increases the prevalence of particular alleles in sheep and goats and creates unique genetic patterns in the genome of these species. The aim of this study was to identify loci with divergent allelic frequencies in a candidate gene panel of 100 genes using two different approaches (frequentist and Bayesian) to estimate Fst outliers in three different breeds of sheep and goats exposed to H. contortus. Results Our results for sheep populations showed SNPs under selection in C3AR1, CSF3, SOCS2, NOS2, STAT5B, TGFB2 and IL2RA genes using frequentist and Bayesian approaches. For goats, SNPs in CD1D, ITGA9, IL12A, IL13RA1, CD86 and TGFB2 genes were under selection. Common signatures of selection in both species were observed in NOS2, TGFB2 and TLR4 genes. Directional selection was present in all SNPs evaluated in the present study. Conclusions A total of 13 SNPs within 7 genes of our candidate gene panel related to H. contortus exposure were identified under selection in sheep populations. For goats, 11 SNPs within 7 genes were identified under selection. Results from this study support the hypothesis that resistance to H. contortus is likely to be controlled by many loci. Shared signatures of selection related to mechanisms of immune protection against H. contortus infection in sheep and goats could be useful targets in breeding programs aimed to produce resistant animals with low FEC.