The cestode Echinococcus multilocularis larva infection causes lethal zoonotic alveolar echinococcosis (AE), a disease posing a great threat to the public health worldwide. This persistent hepatic tumor-like disease in AE patients has been largely attributed to aberrant T cell responses, of which Th1 responses are impeded, whilst Th2 and regulatory T cell responses are elevated, creating an immune tolerogenic microenvironment in the liver. However, the immune tolerance mechanisms are not fully understood. Dendritic cells (DCs) are key cellular components in facilitating immune tolerance in chronic diseases, including AE. Here, we demonstrate that indoleamine 2,3-dioxygenase 1-deficient (IDO1^-/-) mice display less severe AE as compared to wild-type (WT) mice during the infection. Mechanistically, IDO1 prevents optimal T cells responses by programming DCs into a tolerogenic state. Specifically, IDO1 prevents the maturation and migration potential of DCs, as shown by the significantly enhanced expression of the antigen-presenting molecule (MHC II), costimulatory molecules (CD80 and CD86), and chemokine receptors (CXCR4 and CCR7) in infected IDO1^-/- mice as compared to infected wild-type mice. More importantly, the tolerogenic phenotype of DCs is partly reverted in IDO1^-/- mice, as indicated by enhanced activation, proliferation, and differentiation of both CD4⁺ and CD8⁺ - T cells upon infection with Echinococcus multilocularis, in comparison with WT mice. Interestingly, in absence of IDO1, CD4⁺ T cells are prone to differentiate to effector memory cells (CD44⁺CD62L^-); in contrast, CD8⁺ T cells are highly biased to the central memory phenotype (CD44⁺CD62L⁺). Overall, these data are the first to demonstrate the essential role of IDO1 signaling in inducing immunosuppression in mice infected with Echinococcus multilocularis.

Hypoderma bovis and H. sinense (Diptera: Oestridae) mainly parasitise cattle and yaks. The two parasites are pathogenic and cause economic losses that result from reduced amounts of livestock products, including milk, meat, and skin. Genetic diversity and population genetic structure of H. bovis and H. sinense have not been evaluated, but could be used to inform appropriate strategies to control these parasites. We cloned and sequenced part of the mitochondrial cytochrome c oxidase subunit I (COI) gene from 60 H. bovis isolates and 52 H. sinense isolates from five locations in Qinghai Province, China, to identify polymorphisms, and infer their phylogenetic relationships, historical population expansions, and divergence time. We identified 17 COI haplotypes from the H. bovis samples, and 23 COI haplotypes from the H. sinense samples. The haplotype and nucleotide diversities were 0.738 and 0.00202 for H. bovis, and 0.867 and 0.00300 for H. sinense, respectively, which indicates rich genetic diversity in H. bovis and H. sinense populations. Bayesian phylogenetic analysis revealed that the two species are monophyletic, and geographical structuring of haplotypes was significantly different in H. sinense (P < 0.05), but not H. bovis. Neutrality tests and mismatch distribution statistical analysis revealed that populations of the two species have undergone demographic expansions. The divergence three Hypoderma spp. (H. bovis, H. lineatum, and H. sinense) was estimated to have occurred approximately 4.5 million years ago (Mya), which indicates that the rapid uplift of the Qinghai-Tibetan Plateau during the late Miocene-Pliocene was associated with divergence of Hypoderma species. Results of the present study revealed that both H. bovis and H. sinense displayed high genetic diversity and widespread population genetic differentiation within and among populations; these data, along with the molecular phylogeny, demographic history, and divergence time estimation, provide new insight into evolutionary history of these species. These findings will help elucidate speciation in Hypoderma and provide theoretical basis for epidemiological surveillance and control of these species on the Qinghai-Tibetan Plateau.

Background: The schizothoracine fishes, an excellent model for several studies, is a dominant fish group of the Qinghai-Tibet Plateau (QTP). However, species populations have rapidly declined due to various factors, and infection with Echinorhynchus gymnocyprii is cited as a possible factor. In the present study, the molecular characteristics of E. gymnocyprii in four species of schizothoracine fishes from the QTP were explored. Methods: We investigated the infection status of E. gymnocyprii in 156 schizothoracine fishes from the upper Yangtze River, upper Yellow River, and Qinghai Lake in Qinghai Province, China. The complete internal transcribed spacer (ITS) of the ribosomal RNA (rRNA) gene and part of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of 35 E. gymnocyprii isolates from these fishes were sequenced and their characteristics analyzed. In addition, we inferred phylogenetic relationships of the E. gymnocyprii populations based on the rRNA-ITS and cox1 sequences. Results: The total prevalence of E. gymnocyprii in schizothoracine fishes was 57.69% (90/156). However, the prevalence among different species as well as that across the geographical locations of the schizothoracine fishes was significantly different. The results of sequence analysis showed that the four E. gymnocyprii populations from different hosts and regions of Qinghai Province were conspecific, exhibiting rich genetic diversity. Phylogenetic analysis based on rRNA-ITS and cox1 sequences supported the coalescence of branches within E. gymnocyprii; the cox1 gene of E. gymnocyprii populations inferred some geographical associations with water systems. In addition, three species of schizothoracine fishes were recorded as new definitive hosts for E. gymnocyprii. Conclusions: To the best of our knowledge, this is the first molecular description of E. gymnocyprii populations in schizothoracine fishes from the Qinghai-Tibet Plateau that provides basic data for epidemiological surveillance and control of acanthocephaliasis to protect endemic fish stocks.