Metagenomics and Innate Immunity - A Unique Partnership or a Battlefield?

Abstract

ery of new pathogenic microbes [5] and the prediction of responses to therapy, even in noninfectious diseases such as atherosclerosis [6] . This issue of the Journal of Innate Immunity focuses on metagenomics. We have pleasure in presenting three publications specially selected for this theme issue. They focus on the skin, intestinal and lung microbiomes in diseases such as chronic mucocutaneous candidiasis, cirrhosis and pneumonia. Smeekens et al. [7] hypothesized that the STAT1/ STAT3 mutations which lead to chronic mucocutaneous candidiasis would also change skin and mucosal microbiomes. Using 16S rRNA sequencing, the authors found that the skin of such patients had more Gram-negative bacteria (especially Acinetobacter ) and less Corynebacterium than that of healthy controls. When they exposed leukocytes to Acinetobacter , the innate immune response (cytokine expression) to Candida was suppressed. Could this relationship be causal, or at least contributory? In other words, it appears that Acinetobacter tolerizes the host to the presence of Candida . One interpretation of these results is that alterations in the bacterial community, as a result of STAT1/STAT3, lead to more Acinetobacter within the dermal microbiome and thereby increase the risk of Candida infection. This link may shed light on the association between fungal infection and the prior use of antibiotics, an event well-known to alter bacterial communities. The innate immune system is the interface through which the host and micro-organisms influence human health and disease, and it is this interaction which serves as the foundation of metagenomics. We propose that metagenomics will provide novel mechanistic insight and potential therapeutics for both classic infectious disease and what we now consider to be noninfectious diseases. Metagenomics is the evaluation of the genomics of heterogeneous organisms, most often microbes and humans. The metagenomic era started with the genomic description of the microbial community of the human host [1] . Interestingly, the majority of organisms in humans that are detected by genomics are not cultured in the laboratory [2] . The large genomic differences between organisms account for critical microbial characteristics including virulence, antibiotic resistance and host/species adaptation. In contrast to humans whose predominantly noncoding DNA remains a puzzle, about 90% of the microbial genome codes for protein and structural RNA; this is a remarkably efficient structure/function relationship [3] . Although compact genomes facilitate research, the human fecal microbial community has over 500,000 unique genes and over 3 million genes in total – some 150 times the human genome [4] ! Through integrating this emerging microbial data with that of the host response, metagenomics could be used for the early accurate diagnosis of infections (a diagnostic biomarker), the discovPublished online: February 12, 2014 Journal of Innate Immunity