Bağırsak Mikrobiyotası ve Toll Benzeri Reseptörler Arasındaki İlişki: Bağışıklık ve Metabolizma

İntestinal kanal, mikrobiyota ile simbiyotik bir ilişkinin oluşmasına izin veren ve mikroorganizmaların invazyonunu kısıtlayan çeşitli stratejiler geliştirmiştir. Toll benzeri reseptörler (TLR), makrofajlar, dendritik hücreler (DC'ler), T lenfositler ve bağırsak epitel hücreleri dahil olmak üzere çeşitli hücre tiplerinde ifade edilen reseptörlerdir. Patojenlere özgü ve hayatta kalmaları için gerekli olan patojen ilişkili moleküler modelleri (MAMP) tanıyan patojen tanıma reseptörleri (PRR'ler) olarak görev yapmaktadırlar. İnsanda bağırsak mikrobiyotası ile bağırsak epitel hücreleri ve bağışıklık hücreleri üzerindeki TLR'ler arasındaki etkileşimler, bağışıklık sisteminin homeostazının korunmasına destek olmaktadırlar. TLR ilişkili yolaklar enerjiyi bağışıklık yanıtına ayırmak için bağışıklık hücrelerindeki içsel metabolizmayı düzenlemektedir. TLR2 aktivasyonu ile anti-inflamatuar yanıt sonrası kommensal bakteriler “patojenik olmayan” olarak tanınmaktadır. TLR4 gen ifadesi, obez veya tip 2 diyabet hastalarının adipoz doku, periferik kan veya kas dokusu örneklerinde ve obez farelerin adipoz dokularında artmakta ve insülin direnci ile ilişkili olmaktadır. TLR5 yoksun farelerin mikrobiyota kompozisyonlarındaki değişikliklerle ilişkili olan insülin direnci ve artan adipozite dahil olmak üzere metabolik sendrom geliştirmeye eğilimli oldukları bildirilmiştir. Ayrıca TLR antagonistlerinin kullanımı ile immünosupresyonun sağladığı faydalı etkiler metabolik ve kardiyovasküler hastalıklar için araştırılmaya devam etmektedir. Genetik ve çevre etkisiyle bağırsak mikrobiyotasındaki değişiklikler, sorunlu konak bağışıklık tepkisine neden olabilmekte ve mikrobiyota manipülasyonları ile hastalarda mikrobiyotanın yeniden programlanması erişilebilir ve ümit verici tedavi şekilleri sunabilmektedir. Bu nedenle, mikrobiyota ve bağışıklık sistemi arasındaki ilişkinin metabolik parametreleri nasıl düzenleyeceğini anlamak, metabolik hastalıkların tedavisinde ilerlemeler sağlayabilecektir.

Anahtar Kelimeler:

Bağırsak mikrobiyotası, TLR, metabolizma, bağışıklık

The Relationship Between Intestinal Microbiota and Toll-Like Receptors: Immunity and Metabolism

The intestinal tract has developed various strategies that allow a symbiotic relationship with the microbiota and restrict the invasion of microorganisms. Toll-like receptors (TLRs) are expressed in a variety of cell types, including macrophages, dendritic cells (DCs), T lymphocytes, and intestinal epithelial cells. TLRs act as pathogen recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (MAMP) specific to pathogens and essential for their survival. Interactions between intestinal microbiota in humans and TLRs on intestinal epithelial cells and immune cells support the maintenance of the homeostasis of the immune system. TLR-related pathways regulate intrinsic metabolism in immune cells to allocate energy to immune response. Commensal bacteria are recognized as "non-pathogenic" after anti-inflammatory response with TLR2 activation. TLR4 expression is increased in adipose tissue, peripheral blood or muscle tissue samples of obese or type 2 diabetes patients and in adipose tissues of obese mice and is associated with insulin resistance. TLR5-deficient mice have been reported to be prone to developing the metabolic syndrome including insulin resistance and increased adiposity, which is associated with changes in microbiota composition. In addition, the beneficial effects of immunosuppression with the use of TLR antagonists continue to be investigated for metabolic and cardiovascular diseases. The intestinal microbiota changes due to genetics and environmental influences can cause host immune response problems and certain microbiota manipulations and reprogramming of microbiota in patients can offer accessible and promising treatment options. Therefore, it is important to understand how the relationship between the microbiota and the immune system will regulate metabolic parameters which could lead to advances in the treatment of metabolic diseases.

Keywords:

Intestinal microbiota, TLR, metabolism, immunity,

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