Together with various hosts and environments, ubiquitous microbes interact closely with each other forming an intertwined system or community. Of interest, shifts of the relationships between microbes and their hosts or environments are associated with critical diseases and ecological changes. While advances in high-throughput Omics technologies offer a great opportunity for understanding the structures and functions of microbiome, it is still challenging to analyse and interpret the omics data. Specifically, the heterogeneity and diversity of microbial communities, compounded with the large size of the datasets, impose a tremendous challenge to mechanistically elucidate the complex communities. Fortunately, network analyses provide an efficient way to tackle this problem, and several network approaches have been proposed to improve this understanding recently. Here, we systemically illustrate these network theories that have been used in biological and biomedical research. Then, we review existing network modelling methods of microbial studies at multiple layers from metagenomics to metabolomics and further to multi-omics. Lastly, we discuss the limitations of present studies and provide a perspective for further directions in support of the understanding of microbial communities.
Highlights d CT229 recruits Rab GTPases and Rab effectors to the periphery of the inclusion d The CT229 SNARE-like domain is necessary for binding and recruiting Rab GTPases d CT229 and Rab GTPases are required to recruit Tfn to the periphery of the inclusion d CT229 also recruits M6PR-containing vesicles to the vicinity of the inclusion
IL-35 is an immunosuppressive cytokine with roles in cancer, autoimmunity, and infectious disease. In the conventional model of IL-35 biology, the p35 and Ebi3 domains of this cytokine interact with IL-12Rβ2 and gp130, respectively, on the cell surface of regulatory T and regulatory B cells, triggering their suppression of Th cell activity. Here we use a human IL-12 bioactivity reporter cell line, protein binding assays, and primary human Th cells to demonstrate an additional mechanism by which IL-35 suppresses Th cell activity, wherein IL-35 directly inhibits the association of IL-12 with its surface receptor IL-12Rβ2 and downstream IL-12–dependent activities. IL-12 binding to the surface receptor IL-12Rβ1 was unaffected by IL-35. These data demonstrate that in addition to acting via regulatory T and regulatory B cells, human IL-35 can also directly suppress IL-12 bioactivity and its interaction with IL-12Rβ2.
SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig), as generated by the immune system following infection or vaccination, has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG) and inhibitory capacity in asymptomatic individuals between Jan 2021 and May 2022. These data were generated as part of a large university COVID monitoring program and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data demonstrate that COVID vaccines achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.
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