Amrita Institute of Medical Sciences, Research Centre for Nanoscience and Molecular Medicine, AIMS - Ponekkara, Edapally, Cochin, Kerala 682041, India.
Microbiol Res. 2013 Aug 25;168(7):396-406. doi: 10.1016/j.micres.2013.02.005. Epub 2013 Apr 8.
The innate immune system constitutes the first line of defence against invading microbes. The basis of this defence resides in the recognition of defined structural motifs of the microbes called "Microbial associated molecular patterns" that are absent in the host. Cell wall, the outer layer of both bacterial and fungal cells, a unique structure that is absent in the host and is recognized by the germ line encoded host receptors. Nucleotide oligomerization domain proteins, peptidoglycan recognition proteins and C-type lectins are host receptors that are involved in the recognition of bacterial cell wall (usually called peptidoglycan), whereas fungal cell wall components (N- and O-linked mannans, β-glucans etc.) are recognized by host receptors like C-type lectins (Dectin-1, Dectin-2, mannose receptor, DC-SIGN), Toll like receptors-2 and -4 (TLR-2 and TLR-4). These recognitions lead to activation of a variety of host signaling cascades and ultimate production of anti-microbial compounds including phospholipase A2, antimicrobial peptides, lysozyme, reactive oxygen and nitrogen species. These molecules act in cohort against the invading microbes to eradicate infections. Additionally pathogen recognition leads to the production of cytokines, which further activate the adaptive immune system. Both pathogenic and commensal bacteria and fungus use numerous strategies to subvert the host defence. These strategies include bacterial peptidoglycan glycan backbone modifications by O-acetylation, N-deacetylation, N-glycolylation and stem peptide modifications by amidation of meso-Diaminopimelic acid; fungal cell wall modifications by shielding the β-glucan layer with mannoproteins and α-1,3 glucan. This review focuses on the recent advances in understanding the role of bacterial and fungal cell wall in their innate immune recognition and evasion strategies.
先天免疫系统是抵御入侵微生物的第一道防线。这种防御的基础在于识别微生物的特定结构模式,这些结构模式被称为“微生物相关的分子模式”,在宿主中不存在。细菌和真菌细胞的外层细胞壁是一种独特的结构,在宿主中不存在,被胚系编码的宿主受体识别。核苷酸寡聚化结构域蛋白、肽聚糖识别蛋白和 C 型凝集素是参与识别细菌细胞壁(通常称为肽聚糖)的宿主受体,而真菌细胞壁成分(N-和 O-连接的甘露聚糖、β-葡聚糖等)则被宿主受体如 C 型凝集素(Dectin-1、Dectin-2、甘露糖受体、DC-SIGN)、Toll 样受体-2 和 -4(TLR-2 和 TLR-4)识别。这些识别导致各种宿主信号级联的激活,并最终产生抗微生物化合物,包括磷脂酶 A2、抗菌肽、溶菌酶、活性氧和氮物种。这些分子协同作用,对抗入侵的微生物,以消除感染。此外,病原体识别导致细胞因子的产生,进一步激活适应性免疫系统。致病性和共生细菌和真菌都使用多种策略来颠覆宿主防御。这些策略包括细菌肽聚糖聚糖主链的 O-乙酰化、N-去乙酰化、N-糖基化和通过 meso-Diaminopimelic 酸的酰胺化修饰茎肽;真菌细胞壁的修饰通过用甘露糖蛋白和α-1,3 葡聚糖屏蔽β-葡聚糖层。本综述重点介绍了近年来对细菌和真菌细胞壁在先天免疫识别和逃避策略中的作用的理解进展。