The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut-lung axis. Although the gut-lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adapter ASC and assembly of an ASC speck. ASC specks recruit and activate caspase-1, which induces IL-1β cytokine maturation and pyroptotic cell death. Here we show that after pyroptosis ASC specks accumulate in the extracellular space, where they promote further IL-1β maturation. In addition, phagocytosis of ASC specks induces lysosomal damage, nucleation of soluble ASC as well as caspase-1 and IL-1β activation in the recipient cell. ASC specks appear in bodily fluids from inflamed tissues and autoantibodies against ASC specks develop in patients and animals with autoimmune pathologies. Together, these findings reveal extracellular functions of ASC specks and a novel form of cell-to-cell communication.

BackgroundOur view of host-associated microbiota remains incomplete due to the presence of as yet uncultured constituents. The Bacteroidales family S24-7 is a prominent example of one of these groups. Marker gene surveys indicate that members of this family are highly localized to the gastrointestinal tracts of homeothermic animals and are increasingly being recognized as a numerically predominant member of the gut microbiota; however, little is known about the nature of their interactions with the host.ResultsHere, we provide the first whole genome exploration of this family, for which we propose the name “Candidatus Homeothermaceae,” using 30 population genomes extracted from fecal samples of four different animal hosts: human, mouse, koala, and guinea pig. We infer the core metabolism of “Ca. Homeothermaceae” to be that of fermentative or nanaerobic bacteria, resembling that of related Bacteroidales families. In addition, we describe three trophic guilds within the family, plant glycan (hemicellulose and pectin), host glycan, and α-glucan, each broadly defined by increased abundance of enzymes involved in the degradation of particular carbohydrates.Conclusions“Ca. Homeothermaceae” representatives constitute a substantial component of the murine gut microbiota, as well as being present within the human gut, and this study provides important first insights into the nature of their residency. The presence of trophic guilds within the family indicates the potential for niche partitioning and specific roles for each guild in gut health and dysbiosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0181-2) contains supplementary material, which is available to authorized users.

Summary Aberrant T‐cell responses underpin a range of diseases, including asthma and allergy and autoimmune diseases. Pivotal immune elements of these diseases are the development of antigen‐specific effector T‐helper type 2 (Th2) cells, Th1 cells, or the recently defined Th17 cells that are associated with the clinical features and disease progression. In order to identify crucial processes in the pathogenesis of these diseases it is critical to understand how the development of these T cells occurs. The phenotype of a polarized T‐cell that differentiates from a naïve precursor is determined by the complex interaction of antigen‐presenting cells with naïve T cells and involves a multitude of factors, including the dominant cytokine environment, costimulatory molecules, type and load of antigen presented and a plethora of signaling cascades. The decision to take the immune response in a certain direction is not made by one signal alone, instead many different elements act synergistically, antagonistically and through positive feedback loops to activate a Th1, Th2, or Th17 immune response. The elucidation of the mechanisms of selection of T‐cell phenotype will facilitate the development of therapeutic strategies to intervene in the development of deleterious T‐cell responses. This review will focus on the pathways and key factors responsible for the differentiation of the various subsets of effector CD4 T cells. We will primarily discuss what is known of the Th1 and Th2 differentiation pathways, while also reviewing the emerging research on Th17 differentiation.

NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.