Growing, evolving and sticking in a flowing environment: understanding IgA interactions with bacteria in the gut

Abstract

Summary Immunology research in the last 50 years has made huge progress in understanding the mechanisms of anti‐bacterial defense of deep, normally sterile, tissues such as blood, spleen and peripheral lymph nodes. In the intestine, with its dense commensal microbiota, it seems rare that this knowledge can be simply translated. Here we put forward the idea that perhaps it is not always the theory of immunology that is lacking to explain mucosal immunity, but rather that we have overlooked crucial parts of the mucosal immunological language required for its translation: namely intestinal and bacterial physiology. We will try to explain this in the context of intestinal secretory antibodies (mainly secretory IgA), which have been described to prevent, to alter, to not affect, or to promote colonization of the intestine and gut‐draining lymphoid tissues, and where effector mechanisms have remained elusive. In fact, these apparently contradictory outcomes can be generated by combining the basic premises of bacterial agglutination with an understanding of bacterial growth (i.e. secretory IgA‐driven enchained growth), fluid handling and bacterial competition in the gut lumen.

Immunological partners: the gut microbiome in homeostasis and disease

“…Immune control of the microbial populations in the gut is essential to the maintenance of a healthy gut microbiome, and control of gut microbes by gut eosinophils and secretory IgA (sIgA) are the focus of the articles by Singh et al and Hoces et al 4,5 Using mice deficient in eosinophils (i.e. DdblGATA-1 À/À mice), Singh and his colleagues report that an absence of eosinophils did not alter gut architecture, barrier integrity or sIgA levels; however, the loss of eosinophils significantly changed microbial diversity with the greatest effects found in the mucus-associated communities (Fig.…”

“…Looking in more detail into how sIgA regulates microbial colonization, Hoces et al 5 not only discuss the direct interaction between sIgA and gut microbes but also consider the contributions of gut physiology and environment into the seemingly contradictory actions of sIgA in preventing disease but promoting colonization (Fig. 1 ⑤).…”

“…Specifically, they propose a model whereby high microbial densities lead to classical agglutination by sIgA, whereas low bacterial densities promote 'enchained' clonal growth. 5 This enchained growth or clumping provides specific benefits including selective clonal growth and extinction as well as reducing horizontal gene transfer, suggesting an impact on local microbial evolution. 5 By understanding how sIgA regulates microbial communities in the gut, we can better design vaccines or targeted therapeutics that harness the complex activities of sIgA to regulate gut health.…”

“…Taken together, this collection of articles and editorials from Immunology [1][2][3][4][5][6] and Immunology & Cell Biology [7][8][9][10][11][12][13] begin to dissect the complex partnership that has evolved, and continues to evolve, between microbes and humans. The consequences of an unhealthy relationship (i.e.…”

Interactions of the microbiota with the mucosal immune system

“…Notably, while IgA has a welldocumented role in protection from mucosal pathogens, under homeostatic conditions a large proportion of sIgA binds the microbiota [9]. Hoces et al [10] discuss the varied effects that sIgA can have on the members of the gut microbiome, ranging from immune exclusion and growth inhibition to enhanced growth and colonization. Furthermore, exemplifying the need for a cross-disciplinary approach, they emphasize that sIgA-microbial interaction should be analysed in its proper context -the unique environment on the intestinal lumen.…”