Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity

Huang, Zhenxing; Wang, Jianhe; Xu, Xiaoli; Wang, Haishan; Qiao, Yuan; Chu, Wern Cui; Xu, Shengli; Chai, Louis Yi Ann; Cottier, Fabien; Pavelka, Norman; Oosting, Marije; Joosten, Leo A. B.; Netea, Mihai G.; Ng, Carol Yee Leng; Leong, Khai Pang; Kundu, Parag; Lam, Kong-Peng; Pettersson, Sven; Wang, Yue

doi:10.1038/s41564-019-0381-1

Cited by 88 publications

(68 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A previous study similarly reported that peptidoglycan traces found in human serum were responsible for hyphal growth of C. albicans (19). Moreover, while this manuscript was under evaluation, a new study demonstrated the presence of MDP and other peptidoglycan fragments in the blood of multiple warm-blooded animals (31). To directly determine whether our cell culture FCS contained peptidoglycan fragments, HPLC coupled to MS was conducted on two separate batches of FCS, which revealed the presence of multiple muramyl peptides and peptidoglycan-derived peptides (Fig.…”

Section: Er Stress Activates Nod1/2 Through Serum Peptidoglycanmentioning

confidence: 56%

Trace levels of peptidoglycan in serum underlie the NOD-dependent cytokine response to endoplasmic reticulum stress

Molinaro¹,

Mukherjee²,

Flick

et al. 2019

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Er Stress Activates Nod1/2 Through Serum Peptidoglycanmentioning

confidence: 56%

Trace levels of peptidoglycan in serum underlie the NOD-dependent cytokine response to endoplasmic reticulum stress

Molinaro¹,

Mukherjee²,

Flick

et al. 2019

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Along this line, a recent work showed that the circulating bacterial peptidoglycan comes from host microbiota and acts as a natural immune potentiator that tunes the host immune response. The same work also showed that the neutralization of the circulating peptidoglycan suppressed the development of the experimental model of MS (31).…”

Section: Introductionmentioning

confidence: 91%

The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology

et al. 2019

View full text Add to dashboard Cite

The gut barrier consists of several components, including the mucus layer, made of mucins and anti-bacterial molecule, the epithelial cells, connected by tight junction proteins, and a mixed population of cells involved in the interplay with microbes, such as M cells, elongations of “antigen presenting cells” dwelling the lamina propria, intraepithelial lymphocytes and Paneth cells secreting anti-bacterial peptides. Recently, the influence of intestinal permeability (IP) changes on organs far from gut has been investigated, and IP changes in multiple sclerosis (MS) have been described. A related topic is the microbiota dysfunction that underpins the development of neuroinflammation in animal models and human diseases, including MS. It becomes now of interest to better understand the mechanisms through which IP changes contribute to pathophysiology of neuroinflammation. The following aspects seem of relevance: studies on other biomarkers of IP alterations; the relationship with known risk factors for MS development, such as vitamin D deficiency; the link between blood brain barrier and gut barrier breakdown; the effects of IP increase on microbial translocation and microglial activation; the parallel patterns of IP and neuroimmune changes in MS and neuropsychiatric disorders, that afflict a sizable proportion of patients with MS. We will also discuss the therapeutic implications of IP changes, considering the impact of MS-modifying therapies on gut barrier, as well as potential approaches to enhance or protect IP homeostasis.

show abstract

“…A similar scenario is likely for pathobionts within a microbiota that promote pro-inflammatory instead of tolerogenic signals. Several commensal-derived MAMPs such as LPS, peptidoglycan and other, yet to be defined, MAMPs have been shown to activate the innate sensors nucleotide-binding oligomerization domain (NOD)-like receptors and TLRs that in turn contribute to autoimmune and inflammatory diseases 49,50,147,159,160 .…”

mentioning

confidence: 99%

Host–microbiota interactions in immune-mediated diseases

2020

View full text Add to dashboard Cite

The immune system evolved not only to fend off pathogens but also to tolerate beneficial microbiota that evolved to live in symbiosis with the host 1. This is perhaps best exemplified from an immunological viewpoint by the paradigm that not only self but also commensal antigens are recognized by regulatory T (T reg) cells that suppress pathological immune responses 2,3. Thus, under immune homeostasis, the immune system tolerates beneficial commensal bacteria but can respond to these same microbiota during tissue disruption or other homeostatic perturbations 4. Self-non-self discrimination of host antigens is a fundamental process that is established and maintained by well-defined central and peripheral tolerance mechanisms (Box 1). How the host immune system develops and responds to the microbiota remains an immunological conundrum of self-non-self discrimination that is poorly understood. Immune-mediated diseases develop in genetically prone individuals when tolerance mechanisms are broken. These diseases are characterized by immunologically mediated tissue damage that is either directed against self-antigens (autoimmunity), transplanted or transfused antigens (alloimmunity), innocuous environmental agents that are inhaled or ingested (allergy) or in the absence of specific antigens (autoinflammation) (Box 2). It is increasingly appreciated that the microbiota directly and indirectly modulates tolerogenic processes that keep inflammatory responses in check. These responses may occur at barrier surfaces

show abstract

Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity

Cited by 88 publications

References 30 publications

Trace levels of peptidoglycan in serum underlie the NOD-dependent cytokine response to endoplasmic reticulum stress

Trace levels of peptidoglycan in serum underlie the NOD-dependent cytokine response to endoplasmic reticulum stress

The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology

Host–microbiota interactions in immune-mediated diseases

Contact Info

Product

Resources

About