Compartment-specific distribution of human intestinal innate lymphoid cells is altered in HIV patients under effective therapy

Autor: Jürgen K. Rockstroh, Dominik J. Kaczmarek, Christoph Boesecke, Felix Goeser, Tobias van Bremen, Robert Hüneburg, Ulrich Spengler, Carolynne Schwarze-Zander, Steffen Manekeller, Vittorio Branchi, Christian P. Strassburg, Andreas Glässner, Benjamin Krämer, Tobias J. Weismüller, Hans Dieter Nischalke, Jacob Nattermann, Philipp Lutz
Jazyk: angličtina
Rok vydání: 2017
Předmět:
RNA viruses
0301 basic medicine
Gene Expression
HIV Infections
Pathology and Laboratory Medicine
0302 clinical medicine
Immunodeficiency Viruses
Intestinal mucosa
Medicine and Health Sciences
Lymphocytes
Intestinal Mucosa
Biology (General)
skin and connective tissue diseases
education.field_of_study
Gastrointestinal tract
Stomach
Innate lymphoid cell
Human gastrointestinal tract
Intestines
medicine.anatomical_structure
Organ Specificity
Medical Microbiology
Viral Pathogens
Viruses
Anatomy
Pathogens
Research Article
Colon
Duodenum
QH301-705.5
Immunology
Population
Biology
Microbiology
03 medical and health sciences
Esophagus
Immune system
Ileum
Virology
Retroviruses
Genetics
medicine
Humans
education
Interleukin-7 receptor
Microbial Pathogens
Molecular Biology
Innate immune system
Interleukin-7
Lentivirus
Organisms
Biology and Life Sciences
HIV
RC581-607
Immunity
Innate
Gastrointestinal Tract
body regions
030104 developmental biology
Parasitology
Immunologic diseases. Allergy
Digestive System
030215 immunology
Zdroj: PLoS Pathogens, Vol 13, Iss 5, p e1006373 (2017)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: 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.
Author summary Current treatment regimens are very effective in blocking replication of the human immunodeficiency virus (HIV). However, due to ongoing activation of the immune system this often does not fully restore human health. The mechanisms underlying such activation of the immune system are only incompletely understood but are likely to include HIV-induced injury of the gut epithelial barrier and subsequent intrusion of gut flora components into the systemic circulation (microbial translocation). 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. We found that composition of the intestinal ILC pool differs between the specific segments of the digestive tract and is significantly altered in HIV(+) patients. Furthermore, our data suggest a link between dys-regulated intestinal ILCs and loss of intestinal barrier function in HIV infection, thereby allowing for microbial translocation and systemic immune activation. This finding is new and highlights the important role played by the gut immune system in HIV-induced illness.
Databáze: OpenAIRE
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