Understanding and Exploiting Host-Commensal Interactions to Combat Pathogens

Editorial

12 November 2019

Editorial: Understanding and Exploiting Host-Commensal Interactions to Combat Pathogens

Sudhanshu Shekhar

Fernanda Cristina Petersen

and

Xi Yang

2,782 views

0 citations

Editors

Sudhanshu Shekhar

Laboratory of Gnotobiology, Institute of Microbiology (ASCR)

Fernanda Cristina Petersen

University of Oslo

Xi Yang

University of Manitoba

Impact

Mini Review

07 August 2019

Infectious Threats, the Intestinal Barrier, and Its Trojan Horse: Dysbiosis

Simona Iacob

and

Diana Gabriela Iacob

The ecosystem of the gut microbiota consists of diverse intestinal species with multiple metabolic and immunologic activities and it is closely connected with the intestinal epithelia and mucosal immune response, with which it builds a complex barrier against intestinal pathogenic bacteria. The microbiota ensures the integrity of the gut barrier through multiple mechanisms, either by releasing antibacterial molecules (bacteriocins) and anti-inflammatory short-chain fatty acids or by activating essential cell receptors for the immune response. Experimental studies have confirmed the role of the intestinal microbiota in the epigenetic modulation of the gut barrier through posttranslational histone modifications and regulatory mechanisms induced by epithelial miRNA in the epithelial lumen. Any quantitative or functional changes of the intestinal microbiota, referred to as dysbiosis, alter the immune response, decrease epithelial permeability and destabilize intestinal homeostasis. Consequently, the overgrowth of pathobionts (Staphylococcus, Pseudomonas, and Escherichia coli) favors intestinal translocations with Gram negative bacteria or their endotoxins and could trigger sepsis, septic shock, secondary peritonitis, or various intestinal infections. Intestinal infections also induce epithelial lesions and perpetuate the risk of bacterial translocation and dysbiosis through epithelial ischemia and pro-inflammatory cytokines. Furthermore, the decline of protective anaerobic bacteria (Bifidobacterium and Lactobacillus) and inadequate release of immune modulators (such as butyrate) affects the release of antimicrobial peptides, de-represses microbial virulence factors and alters the innate immune response. As a result, intestinal germs modulate liver pathology and represent a common etiology of infections in HIV immunosuppressed patients. Antibiotic and antiretroviral treatments also promote intestinal dysbiosis, followed by the selection of resistant germs which could later become a source of infections. The current article addresses the strong correlations between the intestinal barrier and the microbiota and discusses the role of dysbiosis in destabilizing the intestinal barrier and promoting infectious diseases.

16,551 views

118 citations

Diet and immune activity load (allergies, cancer, other illness, etc.) determine host intestinal integrity toward invading pathogens. Diet affects intestinal integrity directly by stimulating IECs, ILCs, and microbial communities, and indirectly through microbial fermentation by-products (SCFAs, H2S, etc.). A healthy individual following a balanced diet to maintain symbiosis between host and microbial populations has enhanced intestinal integrity with a thick inner and outer mucus layer that retains AMPs and other compounds to protect the host against pathogen colonization (A). A diseased host with heightened immune activity maintains symbiosis by consuming dietary components that protect and boost host innate defenses (IgA, AMPs, mucus, fucosylation) and adaptive immune responses to prevent pathogen colonization (B). Whereas, diseased individuals with heightened immune activity consuming a poor diet are more susceptible to enteric infections due to impaired host defenses that cannot control the dysbiotic intestinal environment (C).

Review

06 August 2019

Diet-Microbe-Host Interactions That Affect Gut Mucosal Integrity and Infection Resistance

Andrew J. Forgie

, 1 more and

Benjamin P. Willing

9,227 views

62 citations

Review

04 July 2019

The Commensal Microbiota and Viral Infection: A Comprehensive Review

Na Li

, 3 more and

Jin-Lian Hua

The human body is inhabited by a diverse microbial community that is collectively coined as commensal microbiota. Recent research has greatly advanced our understanding of how the commensal microbiota affects host health. Among the various kinds of pathogenic infections of the host, viral infections constitute one of the most serious public health problems worldwide. During the infection process, viruses may have substantial and intimate interactions with the commensal microbiota. A plethora of evidence suggests that the commensal microbiota regulates and is in turn regulated by invading viruses through diverse mechanisms, thereby having stimulatory or suppressive roles in viral infections. Furthermore, the integrity of the commensal microbiota can be disturbed by invading viruses, causing dysbiosis in the host and further influencing virus infectivity. In the present article, we discuss current insights into the regulation of viral infection by the commensal microbiota. We also draw attention to the disruption of microbiota homeostasis by several viruses.

Mechanisms underlying the suppression of influenza virus infection by the commensal microbiota. During the influenza virus infection, organisms of the commensal microbiota, as well as their components (i.e., various TLR ligands) or metabolites (i.e., desaminotyrosine) activate the inflammasome, resulting in IL-1β and IL-18 production. The production of these two cytokines induces the migration of dendritic cells from the lung to the draining lymph nodes, where they act as antigen-presenting cells to prime virus-specific B cells, CD4+ T cells, CD8+ T cells, and macrophages. In addition, dendritic cells also secrete type I and type II interferons to stimulate the activation of T cells or macrophages. As a result, these effector cells secrete virus-specific antibodies or inflammatory cytokines or exert direct virus-killing effects to suppress the infection process of the influenza virus.

33,402 views

240 citations

Mini Review

31 May 2019

Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens

Rabia Khan

, 1 more and

Sudhanshu Shekhar

A diverse community of trillions of commensal bacteria inhabits mucosal and epidermal surfaces in humans and plays an important role in defense against pathogens, including respiratory pathogens. Commensal bacteria act on the host's immune system to induce protective responses that prevent colonization and invasion by pathogens. On the other hand, these bacteria can directly inhibit the growth of respiratory pathogens by producing antimicrobial products/signals and competing for nutrients and adhesion sites. Such mechanisms preserve the niche for commensal bacteria and support the host in containing respiratory infections. Herein, we discuss current evidence on the role of commensal bacteria in conferring protection against respiratory pathogens and the underlying mechanisms by which these bacteria do so. A deeper knowledge of how commensal bacteria interact with the host and pathogens might provide new insights that are poised to aid in the development of vaccines and therapeutics that target infectious diseases.

85,964 views

136 citations

Gut microbiota enhance the expression of IL-22 against invading pathogens. IL-22 is important in maintaining the integrity of mucosal barriers and can be produced by many different types innate immune cells, which induce the expression of various antimicrobial proteins, including lipocalin-2, calprotectin, C-type lectins, S100A8, S100A9, and so on to clear pathogens. Increasing evidence identified that gut microbiota enhances the expression of IL-22 to protect the host against pathogens. The results show that gut microbiota utilize tryptophan as an energy source and produce a metabolite, indole-3-aldehyde (IAld), which in turns activated Ahr on innate immune cells. Once activated, innate immune cells will secrete IL-22, which protects the host against opportunistic pathogens by reducing their colonization.

Review

29 March 2019

Interactions Between the Gut Microbiota and the Host Innate Immune Response Against Pathogens

Hong-Yu Cheng

, 2 more and

Wen-Tao Ma

22,440 views

181 citations

HDAC3 regulates epithelial Clec2e expression and pathogen adherence. (A) ChIP-seq for H3K9Ac in primary IECs isolated from the large intestine of HDAC3FF and HDAC3ΔIEC mice. (B) ChIP-qPCR for H3K9Ac in Clec2e in IECs from the small intestine. (C) Clec2e expression in IECs from large and small intestine of HDAC3FF and HDAC3ΔIEC mice. (D) C. rodentium CFUs in stool at day 6 post infection. (E) Fluorescence microscopy of colon from HDAC3FF and HDAC3ΔIEC mice infected with GFP-C. rodentium. (Green: GFP-C. rodentium, Red: Phalloidin, Blue: DAPI). Scale bars, 25 μm. (F) MFI of GFP-C. rodentium infected intestinal organoids derived from HDAC3FF and HDAC3ΔIEC mice. Data are representative of at least 2 independent experiments with 3–4 mice per group. Results are mean ± SEM. *p < 0.05.

Original Research

07 May 2019

Microbiota Inhibit Epithelial Pathogen Adherence by Epigenetically Regulating C-Type Lectin Expression

Vivienne Woo

, 4 more and

Theresa Alenghat

8,824 views

24 citations

Original Research

28 March 2019

Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

Yue Gao

, 7 more and

Hong Wang

6,717 views

29 citations

Original Research

31 May 2019

Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Uses the VraSR Regulatory System to Modulate Autophagy for Increased Intracellular Survival in Macrophage-Like Cell Line RAW264.7

Yuanyuan Dai

, 5 more and

Jiabin Li

4,249 views

11 citations

Review

08 March 2019

Microbiome Dependent Regulation of Tregs and Th17 Cells in Mucosa

Pushpa Pandiyan

, 4 more and

Jochen Huehn

Mammals co-exist with resident microbial ecosystem that is composed of an incredible number and diversity of bacteria, viruses and fungi. Owing to direct contact between resident microbes and mucosal surfaces, both parties are in continuous and complex interactions resulting in important functional consequences. These interactions govern immune homeostasis, host response to infection, vaccination and cancer, as well as predisposition to metabolic, inflammatory and neurological disorders. Here, we discuss recent studies on direct and indirect effects of resident microbiota on regulatory T cells (T_regs) and Th17 cells at the cellular and molecular level. We review mechanisms by which commensal microbes influence mucosa in the context of bioactive molecules derived from resident bacteria, immune senescence, chronic inflammation and cancer. Lastly, we discuss potential therapeutic applications of microbiota alterations and microbial derivatives, for improving resilience of mucosal immunity and combating immunopathology.

34,759 views

204 citations