Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity

Clarke, Tom; Davis, Kimberly M.; Лысенко, Елена; Zhou, Alice; Yu, Yimin; Weiser, Jeffrey N.

doi:10.1038/nm.2087

Cited by 976 publications

(897 citation statements)

References 31 publications

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“…Because of the lack of direct contact with live microbes, it has long been presumed that the microbiota does not influence these systemic defences. We now know that this assumption is incorrect and that the production and function of cells that constitute systemic defences is greatly influenced by the microbiota 29, 30, 39, 66, 67, 68…”

Section: Host Resistance To Systemic Infection and The Microbiotamentioning

confidence: 99%

“…The resulting agglomeration of immune cells and structures helps to manage and contain the microbiota at the mucosa 23, 24. The microbiota also drives the maturation of systemic immunity beyond the confines of the mucosa, including in major immune tissues such as the bone marrow and spleen 25, 26, 27, 28, 29, 30. The importance of host–microbiota interactions for our health has been highlighted by clinical studies and work with animal models demonstrating that microbiota dysbiosis is associated with diseases and immune dysfunctions in both intestinal and extra‐intestinal tissues.…”

Section: Introductionmentioning

confidence: 99%

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The regulation of host defences to infection by the microbiota

Brown

Clarke

2016

Immunology

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SummaryThe skin and mucosal epithelia of humans and other mammals are permanently colonized by large microbial communities (the microbiota). Due to this life‐long association with the microbiota, these microbes have an extensive influence over the physiology of their host organism. It is now becoming apparent that nearly all tissues and organ systems, whether in direct contact with the microbiota or in deeper host sites, are under microbial influence. The immune system is perhaps the most profoundly affected, with the microbiota programming both its innate and adaptive arms. The regulation of immunity by the microbiota helps to protect the host against intestinal and extra‐intestinal infection by many classes of pathogen. In this review, we will discuss the experimental evidence supporting a role for the microbiota in regulating host defences to extra‐intestinal infection, draw together common mechanistic themes, including the central role of pattern recognition receptors, and outline outstanding questions that need to be answered.

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Section: Host Resistance To Systemic Infection and The Microbiotamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The regulation of host defences to infection by the microbiota

Brown

Clarke

2016

Immunology

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“…For example, dental bacteria can cause episodic bacteremia and release LPS into the circulation and may also seed biofilm formation on orthopaedic implants [29,77,78]. Moreover, there is extensive evidence that PAMPs can translocate from the gastrointestinal tract to distant organs, including the bone marrow, and systemically prime the innate immune system in the absence of infection [14,18,25,28,42,63,70,71,84,101,115]. This translocation of PAMPs from the gut can be increased by minor surgical procedures, such as colonoscopy, a high-fat diet, or even a single high-fat meal [3,14,52,71,84].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

“…The local effects of the PAMPs can also include increased corrosion of titanium surfaces, which in turn can increase PAMP binding to the surface [6]. Alternatively, gut-derived PAMPs could induce chronic low-level inflammation systemically [14,18,25,28,42,52,63,70,71,84,101,115], as appears to occur in the synovium during rheumatoid arthritis [12,106]. In this regard, it has recently been proposed that systemic low-level inflammation may contribute to aseptic loosening [81].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

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“…L'impact du microbiote intestinal n'est pas limité à l'intestin, il s'exerce également à l'échelle systémique des organismes hôtes. Il régule en effet la maturation du système immunitaire [5,6], la croissance post-natale [7,8], et peut même influencer l'activité cérébrale [9,10,48] (➜). Chez l'homme, des perturbations du microbiote intestinal sont associées à une grande variété de pathologies d'ordre métabolique, immunitaire ou même cognitif [11,12].…”

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