Table 3.

Direct (⇑⇑), reverse (⇑⇓) or no (⊗) links of CD and Hp infection.

	⇑⇑	⇑⇓ or ⊗
Clinic	The cases of fresh HP infection in the CD patients and the reports of CD onset right after the carried H. pylori infection both in children and adults were described (Cârdei et al., 2003; Villanacci et al., 2006).	The milder CD forms were found to be more prevalent in HP-positive adults (Villanacci et al., 2006). The data, received in children are contradictory (Guz-Mark et al., 2014; Narang et al., 2016). On a gluten free diet the normalization of the duodenal mucosa was independent of presence/absence of HP both in adults and children (Bardella et al., 2007; Aydogdu et al., 2008).
Genetic	DQA1*03:01 was found to be often in both CD and HP-positive duodenal ulcer patients (Azuma et al., 1995; Mubarak et al., 2013). TNF-308 (G > A) SNP increases risk of CD and persistent HPinfection (Khan et al., 2016). The−336G CD209 allele# associated with a higher HP infection severity/susceptibility might be involved in CD susceptibility in HLA-DQ2 negative patients. (Núñez et al., 2006).	DQA1*0201 allele associated with the high CD risk was significantly rarer in the HP-positive duodenal ulcer patients than in the HP-negative controls (Azuma et al., 1995; Lionetti et al., 2014). HLA-DRB1*0301 and DRB1*07 associated with high CD risk in some ethnic groups are involved in the of some HPproteins recognition and in subsequent activation of gastric T cells within the framework of antiinfective immune response (Bilbao et al., 2002; talová et al., 2002; Bergman et al., 2005).
Gastrointestinal functions	Hp infection leads to the abnormal gut permeability, due to increased production of pro-inflammatory cytokines (Caron et al., 2015). At that the subjects with latent CD have an abnormal permeability (Peña and Crusius, 1998; Sapone et al., 2011) The abnormal mucosal permeability increases the gluten availability for the gluten-specific lymphocyte clones in the Peyer's Plaques.	CD patients were found to have high basal and stimulated acid-forming function, while a comfortable microenvironment for HPincludeЪɪhypochlorhydria (Il'chenko et al., 1991; Savarino et al., 1999; Krums et al., 2011; Harris et al., 2013). Indeed, HPcan only survive for minutes in the stomach lumen (pH of 1–2) and must quickly migrate to the gastric epithelial surface (Schreiber et al., 2005).
Innate immune	–	Hpcolonizes the gastric mucosa by adhering to the mucous epithelial cells via the fucosylated blood group antigens H-type 1 and Leb (Magalhães and Reis, 2010). In principle, the typical for CD immaturity of the gastrointestinal tractincludes weak functions of the mucosal barrier and a lack of bacteria colonization (Forchielli and Walker, 2005). However, single publications indicated no features of the glycocalyx/mucous layer carbohydrate structures in CD (Toft-Hansen et al., 2013).
	The inflammatory cells in the Hpinfection in epithelium and lamina propria express inducible NO-synthase with excess free radicals due to the alterations and exacerbation of inflammation with impaired regeneration processes (Cherdantseva et al., 2014). The similar events occur after gluten exposure in the gastrointestinal mucosa of gluten-sensitive patients, being due to the in injury of the small-intestinal tissue (Holmgren Peterson et al., 1998; Niveloni et al., 2000).	Increased tissues concentration of nitric oxide metabolites in CD might have a protective effect against Hp (Gobert and Wilson, 2016). At the same time Hp uses diverse strategies to promote its survival. All Hpstrains encode proteins important for detoxifying reactive oxygen species and its arginase limits NO production by macrophage-, neutrophil- and epithelial cell-derived nitric oxide synthase (Salama et al., 2013). So, the passing suppression of CD- caused inflammation by Hp is quite possible. Defensins' levels are increased in CD mucosa (Vordenbäumen et al., 2010). During Hp infections, these cationic peptides with antimicrobial properties play a pivotal role in the innate immune responses and are able to eradicate the bacteria (Pero et al., 2017). It should be noted that according to some data, HP strains were resistant to these factors (Nuding et al., 2013).
	Hp induces apoptosis of gastric epithelial cells directly and via modulation TRAIL-mediated apoptosis signaling (Tsai and Hsu, 2010). This effect might contribute to epithelial apoptosis and villous atrophy—CD hallmark (Shalimar et al., 2013).	In Hp positive CD patients a significantly lower prevalence of atrophic gastritis was observed when compared with Hp negative ones (Santarelli et al., 2006). That might be due to the expression of several DNA repair proteins in the inflamed tissue accumulating damaged host DNA (Salama et al., 2013). On the other hand, Hp can gain a foothold in gastrointestinal tract only in the mild CD cases. It is in line with the data, demonstrating the higher inflammation in correlation with lower bacterial upload (Salama et al., 2013).
	Proinflammatory cytokine production in the framework of anti Hp immune reaction might be due to CD triggering (Crabtree, 1996).	Increased local levels of proinflammatory cytokines in CD might have a protective effect against the fresh Hp infection (Eiró et al., 2012; Di Sabatino et al., 2016).
	Gastroduodenal response to chronic Hp infection include IL-8secretion, that being due to neutrophil migration and activation (Crabtree, 1996). These events might trigger CD, as the cells play important role in CD pathogenesis (Lammers et al., 2015).	The increased infiltration by activated neutrophil was demonstrated in CD mucosa (Hällgren et al., 1989). That might have a protective effect while HPexposure.
Adaptive immunity	After the challenge of 4-weeks aged (infants) and 6-weeks aged (adults) mice with HP strain T-cell activation in the gastric samples was demonstrated including the pathways for pro-inflammatory molecules (nitric oxide, iNOS), this effect increased over time (Kienesberger et al., 2016).	Hp re-programs dendritic cells playing a crucial role in Hp recognition toward a tolerance-promoting phenotype; HP-exposed DCs fail to induce effector T-cell responses of the Th1 and Th17 type in vitro and in vivo; instead, they preferentially induce the expression of the Treg-specific transcription factor FoxP3, the surface marker CD25 and the anti-inflammatory cytokine IL-10 in naive T-cells (Salama et al., 2013). The role of this effect in protection from protection against allergies, asthma and inflammatory bowel diseases, was demonstrated (Oertli and Müller, 2012). Besides, at least two virulence factors are known to inhibit human T-cells. VacAvia β2 integrin reception inhibits T-cell proliferation and prevents nuclear translocation of the T-cell transcription factor NF-AT and its subsequent transactivation of T-cell-specific immune response genes. The other virulence determinant—γ-glutamyl-transpeptidase blocks proliferation of T-cells (Salama et al., 2013). As the interaction of the virulent molecules with T-cells is non-specific, a bystander gluten-specific T-cell repression is quite possible. It's a purely speculativehypothesis. No one research was published on this issue.
Microbiome	Lactobacillus species (Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus reuteri) were able to inhibit Hpgrowth in vitro (Zaman et al., 2014; Delgado et al., 2015). Streptococcus mitis, a commensal microorganism of the human stomach, was found to inhibit Hpgrowth and to drive its conversion from a spiral to a coccoidal form (Khosravi et al., 2014). Just the same Lactobacillus and Streptococcus species appeared to be ability to degrade and remove gluten derivatives (Fernandez-Feo et al., 2013; Duar et al., 2015). The impact of these coincidences on both CD and Hp infection remain unclear because (1) the studies of activities were carried using cultivated and then isolated microbes, whereas the glutenase activity of aggregate microbial community as a whole (biofilm) in gut boundary layer may significantly differ from the isolated activity of the individual members of this community; (2) the immunogenicity of the generated peptide fragments might be different that might be due to the opposite effect on CD.

#CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation, Hp infection in particular (Bergman et al., 2006; Núñez et al., 2006). It was found to be overexpressed in the Hp infected gastric epithelial cells and to mediate Th1 differentiation, which may be involved in gastric mucosal injury (Wu et al., 2014).