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Table 1 Summary of the included studies of NETs in intestinal infection

From: The emerging role of neutrophilic extracellular traps in intestinal disease

Pathogen Type of trial The change of NETs Active components of NETs Treatment The role of NETs and its effect to issues changes or cell Mechanisms of antibacterial or non-antibacteri of NETs Frist author, References
Gram-positive bacteria (staphylococcus) Vivo, vitro NET formed rapidly and NETs are released from the nucleus NETs DNA DNase I NETs are crucial to contain an acute invasive infection in vivo NET formation is tightly regulated and requires both Tlr2 and C3 Bryan et al. [35]
Enteropathogenic and Shiga-Toxigenic Escherichia coli(EPEC and STEC) Vivo Firstly reported the formation of DNA NETs in vivo in the intestinal tract. EPEC and STEC infections stimulate the formation of extracellular DNA NETs alonely NETs DNA DNase I NETs were acting as an non-antibacterial host defense. Additing DNase provided protection against the intestinal tissue damage caused by EPEC infection   Crane et al. [55]
methicillin-resistant S. aureus(MRSA) Vivo(WT mice,NE−/− and PAD4−/−mice Intravenous infection with MRSA, leading to rapid a neutrophil-dependent NET formation within the liver sinusoids ExtDNA、NE and histones DNase I Neutrophil recruitment and subsequent NET release destroyed the tight junction between endothelial cells and is associated with profound liver injury But the effectiveness of DNase might be limited in terms of removal of the most dangerous NET components and advocates for inhibition of NET production Elzbieta et al. [56]
Afa/Dr Diffusely Adhering Escherichia coli Vitro NET production by PLB-985 cells infected with the Afa/Dr wild-type (WT) E. coli strain C1845 NET-bound proteases DNase I NETs is actively involved in the antibacterial response of PLB-985 cells against enterovirulent WT C1845 bacteria. But PLB-985-derived NETs might directly contribute to Caco-2/TC7 epithelial cell damage via NET-bound proteases   Marin-Esteban et al. [57]
Pseudomonas aeruginosa Vivo and vitro P. aeruginosa induces the production of NETs in vitro and in vivo and quickly responds and defends against the DNA and histone mediated-antibacterial effects of NETs by stabilizing the outer membrane ExtDNA DNase I, Mg2+ and Ptase DNA backbone of NETs contributes to their bactericidal function. But the spermidine and arn surface modifications contribute to resisting a broad range of antimicrobial components present within NETs, which may protect P. aeruginosa from NET-induced oxidative damage Produced new immune escape mechanisms by sensing and defending against NETs Halverson et al. [58]
Nonpathogenic WT Escherichia coli and its several isogenic mutant Vivo(Lcn KO,mpoko and Nox2KO mice) and vitro Ent-producing Escherichia coli can NETs. Lcn2-deficient BMDNs generated more PMA-induced NETs than did WT BMDNs    The inhibition of neutrophil ROS and NET responses and impairs neutrophil function by enterobactin may confer a survival advantage to Ent-producing Escherichia coli Showed the production of siderophore by E. coli and other bacteria may be a key mechanism that allows them to evade NET-mediated killing Saha et al. [59]
Vibrio cholerae Vivo and vitro V. cholerae induces NET formation and degrades NETs by the activity of two extracellular nucleases Dns and Xds ExtDNA   Dns and Xds mediate evasion of V. cholerae from NETs and lower the susceptibility for extracellular killing in the presence of NETs and enhanced survival of V. cholerae in the presence of NETs, leading to intestinal inflammation Ecluded a new evidence that the innate immune response impacts the colonization of V. cholerae Seper et al. [61]
Entamoeba histolytica trophozoites Vitro Neutrophils that were interacted with E. histolytica trophozoites released NETs. And the presence of both nuclear and mtDNA was detected. NETs were generated independently of NOX2-derived ROS Histone H4, MPO, NE and decondensed DNA DNase I, GSK484 and PMSF NETs caught, immobilized and fragmented E. histolytica trophozoites NETosis occurs rapidly and depends on the viability of amoebas. But mechanism the NETs formation triggered by this parasite and its role in protection or pathogenesis of amoebiasis not yet clarified Ventura-Juarez et al. [65] DíAZ-GODíNEZ et al. [66]
Candida albicans Vivo and vitro Both opsonized and unopsonized C. albicans induce NET formation. NET formation in peritoneal cavity after C. albicans infection NE BB-CI-Amidine and GSK484 Neutrophil killing of unopsonized C. albicans requires dectin-2-mediated NET formation and the NETs restrains C. albicans spread from peritoneal cavity to kidney Unopsonized C. albicans-induced NET formation is independent of NADPH oxidase and mitochondrial ROS and is dependent on PAD4 and dectin-2 enzymatic activity Wu et al. [34] Branzk et al. [68]
Aspergillus fumigatus Vivo and vitro Reutrophils released NETs in response to A. fumigatus hyphae or large aggregated
A. fumigatus conidia but failed to form NETs in response to small single conidia
NE AREG (inhibitor of NE) NETs not only were irrelevant in protecting these mice against the yeast-locked hgc1ΔC. albicans strain but also were detrimental to the host when present in large amounts Selective NETosis was independent of the expression of molecules on the surface of fungi or the enzymatic activity of fungi and was regulated only by differences in microbe size Branzk et al. [68]