Abstract
Innate lymphocyte cells (ILCs), a novel family of innate immune cells are considered to function as key orchestrators of immune defences at mucosal surfaces and to be crucial for maintaining an intact intestinal barrier. Accordingly, first data suggest depletion of ILCs to be involved in human immunodeficiency virus (HIV)-associated damage of the intestinal mucosa and subsequent microbial translocation. However, although ILCs are preferentially localized at mucosal surfaces, only little is known regarding distribution and function of ILCs in the human gastrointestinal tract. Here, we show that in HIV(-) individuals composition and functional capacity of intestinal ILCs is compartment-specific with group 1 ILCs representing the major fraction in the upper gastrointestinal (GI) tract, whereas ILC3 are the predominant population in ileum and colon, respectively. In addition, we present first data indicating that local cytokine concentrations, especially that of IL-7, might modulate composition of gut ILCs. Distribution of intestinal ILCs was significantly altered in HIV patients, who displayed decreased frequency of total ILCs in ileum and colon owing to reduced numbers of both CD127(+)ILC1 and ILC3. Of note, frequency of colonic ILC3 was inversely correlated with serum levels of I-FABP and sCD14, surrogate markers for loss of gut barrier integrity and microbial translocation, respectively. Both expression of the IL-7 receptor CD127 on ILCs as well as mucosal IL-7 mRNA levels were decreased in HIV(+) patients, especially in those parts of the GI tract with reduced ILC frequencies, suggesting that impaired IL-7 responses of ILCs might contribute to incomplete reconstitution of ILCs under effective anti-retroviral therapy. This is the first report comparing distribution and function of ILCs along the intestinal mucosa of the entire human gastrointestinal tract in HIV(+) and HIV(-) individuals.
Highlights
The gastrointestinal (GI) tract is the largest internal extension of the body’s surface and as such is constantly exposed to a myriad of environmental stimuli that include, but are not limited to microbes, dietary products and diverse inorganic materials [1]
Current treatment regimens are very effective in blocking replication of the human immunodeficiency virus (HIV)
This study looks at the distribution and function of innate lymphoid cells (ILCs) in the gut mucosa of HIV(-) and HIV(+) patients as these cells are important for maintaining an intact gut epithelium
Summary
The gastrointestinal (GI) tract is the largest internal extension of the body’s surface and as such is constantly exposed to a myriad of environmental stimuli that include, but are not limited to microbes, dietary products and diverse inorganic materials [1]. To ensure optimal transport of nutrients and fluids, while preventing translocation of commensals and pathogenic microorganisms the intestinal tract is equipped with a highly complex, intrinsic immune system. In this context, innate lymphocyte cells (ILCs), a novel family of innate immune cells, are of special interest as these cells are considered to function as key orchestrators of immune defences at mucosal surfaces and to be crucial for maintaining an intact intestinal barrier [5,6,7]
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