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T follicular regulatory (Tfr) cell is a recently discovered subset of T regulatory (Treg) cells. The main function of Tfr cells is thought to suppress germinal cancer reaction and inhibit B cell proliferation and Ig production. However, recent studies demonstrate that Tfr cells may be required for high-affinity Ig formation during acute virus infections. The role of Tfr cells in breast cancer is not thoroughly investigated. In this study, total circulating CD4 T cells were sorted into CD25+CXCR5− Treg-like, CD25+CXCR5+ Tfr-like, and CD25−CXCR5+ Tfh-like subsets. Data showed that the Tfr-like subset presented intermediate levels of both Foxp3 and Bcl-6, while the Treg-like subset was high in Foxp3 and low in Bcl-6, and the Tfh-like was high in Bcl-6 and low in Foxp3. Of note, the frequencies of Tfr-like and Treg-like cells were significantly elevated in breast cancer (BC) patients than in non-cancer (NC) controls. Tfr-like cells in BC patients also expressed significantly higher levels of Foxp3 than those in NC controls. Neither Treg-like nor Tfr-like cells could support Ig production from naive B cells, while Tfh-like cells potently supported Ig production from naive B cells. Tfr-like cells increased the availability of IL-10, both by directly producing IL-10 and by increasing IL-10 production from B cells. Interestingly, Tfr-like cells increased IL-10 production from B cells synergistically with Tfh cells, but at the same time, significantly reduced Ig production in the Tfh-B cell coculture. These Tfr-mediated effects on Tfh cells were not found in canonical Treg cells. Overall, this study demonstrates several distinctive features in circulating Tfr cells and suggests that Tfr cells may promote the formation of IL-10-producing B cells in BC.
相似文献Astroviruses (AstV) are associated with enteric and systemic disease in mammals and birds. Astroviruses have received increased attention recently as they have been found to be associated with sporadic neurologic disease in mammals including humans. In pigs, porcine astrovirus (PoAstV) can be widely detected and has been grouped in five genotypes (PoAstV1 to PoAstV5). In the present study, we detected multiple PoAstVs in serum samples, nasal swabs, and fecal swabs collected from pigs suffering from respiratory disease or diarrhea but also from asymptomatic pigs, indicating a wide tissue tropism of the identified PoAstV genotypes. Coinfection of different genotypes in the same pig was commonly observed, and within an individual pig a high genetic diversity was observed for viruses belonging to the same PoAstV genotype. Two complete genomes of PoAstV2-WG-R2/2017 and PoAstV4-WG-R2/2017 were successfully obtained and characterized, with genome sizes of 6396 and 6643 nucleotides, respectively. The PoAstV2-WG-R2/2017 genome showed identities of 67.2–77.4% to other known PoAstV2 genomes, and the PoAstV4-WG-R2/2017 genome showed identities of 72.8–80.5% to other known PoAstV4 genomes. The predicted spike domain of open reading frame 2 (ORF2) of these strains showed the highest genetic heterogeneity, with amino acid identities of 13.7–70.9% for PoAstV2-WG-R2/2017 to other known PoAstV2 strains, and identities of 24.4–63.3% for the PoAstV4-WG-R2/2017 to other known PoAstV4 strains. Possible recombination events were identified in each of the two sequences. Two subclades of PoAstV2 and three subclades of PoAstV4 were defined in the present analyses. The obtained data provide further evidence for extraintestinal infectivity of PoAstVs, and confirmed the high genetic diversity of PoAstVs and the coinfection potential of different PoAstV types in a single pig.
相似文献The infection patterns and clinical significance of Enterocytozoon bieneusi and Giardia duodenalis in dairy cattle remain poorly investigated despite their common occurrence. Data on the genetic diversity are also needed to understand the transmission and human-infective potential of the two pathogens. In this study, fecal specimens from 1366 dairy cattle on a large farm were examined for the presence and genotype distribution of E. bieneusi and G. duodenalis by PCR and DNA sequencing. The overall infection rates of E. bieneusi and G. duodenalis were 13.0% and 20.6%, respectively. Pre-weaned calves had significantly higher infection rates of both pathogens than post-weaned and adult cattle (P < 0.001), with peak occurrence of the pathogens in animals of 7–12 weeks. In both pre- and post-weaned calves, animals with diarrhea were 2.1–3.0 times more likely to be infected with either pathogen than those without diarrhea (P < 0.01). The E. bieneusi identified belonged to five genotypes, including J (n = 138), I (n = 21), BEB4 (n = 10), Type IV (n = 1), and a novel genotype CHC17 (n = 1). Genotype J was the dominant one in all age groups, whereas genotype I was only identified in calves of 6–11 weeks. Genotyping of G. duodenalis at three genetic loci identified assemblage E (n = 278), assemblage A (n = 2), and concurrence of the two (n = 1). Altogether, 13, 7 and 10 subtypes of assemblage E were detected at the bg, gdh, and tpi loci, respectively, forming 65 multilocus genotypes. The formation of two major clusters of MLGs in eBURST analysis indicated that intra-assemblage genetic recombination of two dominant MLGs could have led to the high genetic heterogeneity within assemblage E on a single farm. Results of this study provide much needed data on the pathogenicity of E. bieneusi and G. duodenalis in pre- and post-weaned calves. The clinical significance of the two pathogens in dairy cattle warrants further investigations.
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