Symbiotic digestion of lignocellulose in wood-feeding higher termites (family Termitidae) is a two-step process that involves endogenous host cellulases secreted in the midgut and a dense bacterial community in the hindgut compartment. The genomes of the bacterial gut microbiota encode diverse cellulolytic and hemicellulolytic enzymes, but the contributions of host and bacterial symbionts to lignocellulose degradation remain ambiguous. Our previous studies of Nasutitermes spp. documented that the wood fibers in the hindgut paunch are consistently colonized not only by uncultured members of Fibrobacteres, which have been implicated in cellulose degradation, but also by unique lineages of Spirochaetes. Here, we demonstrate that the degradation of xylan, the major component of hemicellulose, is restricted to the hindgut compartment, where it is preferentially hydrolyzed over cellulose. Metatranscriptomic analysis documented that the majority of glycoside hydrolase (GH) transcripts expressed by the fiber-associated bacterial community belong to family GH11, which consists exclusively of xylanases. The substrate specificity was further confirmed by heterologous expression of the gene encoding the predominant homolog. Although the most abundant transcripts of GH11 in Nasutitermes takasagoensis were phylogenetically placed among their homologs of Firmicutes, immunofluorescence microscopy, compositional binning of metagenomics contigs, and the genomic context of the homologs indicated that they are encoded by Spirochaetes and were most likely obtained by horizontal gene transfer among the intestinal microbiota. The major role of spirochetes in xylan degradation is unprecedented and assigns the fiber-associated Treponema clades in the hindgut of wood-feeding higher termites a prominent part in the breakdown of hemicelluloses.

IL-33 is a recently identified IL-1 family cytokine that promotes type 2 immune responses by signaling through the receptor complex consisted of ST2 and IL-1RAcP. Recent study using ST2 KO mice showed that IL-33 mediated signaling is required for the development of innate and adaptive immune responses against pulmonary Cryptococcus neoformans infection, suggesting involvement of IL-33/IL33R system in pulmonary cell-mediated immunity. In contrast, the ST2 KO mice showed normal protective immunity against pulmonary Mycobacterium tuberculosis (Mtb) infection. In this study, we analyzed role of IL-33 in host defense against chronically infected Mtb using IL-33 KO mice. The survival rate of the IL-33 KO mice was similar to that of the wild-type (WT) mice during 1 year observation period. Bacterial burdens of various organs of the IL-33 KO mice on the day 120 were nearly the same as that of the WT mice. In the infected lungs, inflammatory cytokine such as IFN-γ, TNF-α and IL-6, production of the IL-33 KO mice were similar to that of the WT mice. This result indicated that the generation of Th1 cells was not affected in the IL-33 KO mice infected with Mtb. Furthermore, the size of granulomatous lesionss in the lungs of the IL-33 KO mice were similar in comparison to the granulomas that of the WT mice on day 250 of infection. These data strongly support the notion that the lack of IL-33 neither suppress nor enhances protective immunity in the lung after mycobacterial infection.

IL-17 family cytokine is comprised of six members, IL-17A to IL-17F. Recent studies using cytokine- and receptor-deficient mice showed that IL-17A and IL-17F were required for responses to extracellular bacterium K. pneumonia in the lungs and C. rodentium in the colon, respectively. However, the involvement of IL-17A and IL-17F in protective immunity was well not clearly demonstrated in mycobacterial infected lung. In this study, we analyzed role of IL-17A and IL-17F in host defense against chronically infected M. tuberculosis. using IL-17A- and IL-17F-KO mice. The IL-17A-KO mice showed significantly decreased survival rates compared with the wild-type (WT) mice during 250-day observation period. In contrast, survival rate of the IL-17F-KO mice were similar to that of the WT mice. Bacterial burdens of various organs of the IL-17F-KO mice on the day 250 were nearly the same as that in the WT mice. In the infected lungs, the IL-17A-KO mice produced less IFN-γ, TNF and IL-6 in comparison to those from the WT mice, while cytokine production of the IL-17F-KO mice were similar to that of the WT mice. This result indicated that the generation of Th1 cells was impaired in the IL-17A-KO mice but not in the IL-17F-KO mice infected with M. tuberculosis. These data strongly support the notion that the lack of IL-17F neither suppress nor enhances protective immunity in the lung after mycobacterial infection.