Abstract
The defect on Fc gamma receptor IIb (FcγRIIb), the only inhibitory FcγR, has been identified as one of the genetic factors increasing susceptibility to lupus. The prevalence of Helicobacter pylori (HP) and FcγRIIb dysfunction-polymorphisms are high among Asians, and their co-existence is possible. Unfortunately, the influence of HP against lupus progression in patients with lupus is still controversial. In this study, the interactions between these conditions were tested with HP infection in 24-week-old FcγRIIb-/- mice (symptomatic lupus). HP induced failure to thrive, increased stomach bacterial burdens and stomach injury (histology and cytokines) in both wild-type and FcγRIIb-/- mice. While the severity of HP infection, as determined by these parameters, was not different between both strains, antibodies production (anti-HP, anti-dsDNA and serum gammaglobulin) were higher in FcγRIIb-/- mice compared to wild-type. Accordingly, HP infection also accelerated the severity of lupus as determined by proteinuria, serum creatinine, serum cytokines, renal histology, and renal immune complex deposition. Although HP increased serum cytokines in both wild-type and FcγRIIb-/- mice, the levels were higher in FcγRIIb-/- mice. As such, HP also increased spleen weight and induced several splenic immune cells responsible for antibody productions (activated B cell, plasma cell and follicular helper T cell) in FcγRIIb-/- mice, but not in wild-type. These data describe the different systemic responses against localized HP infection from diverse host genetic background. In conclusion, the mutual interactions between HP and lupus manifestations of FcγRIIb-/-mice were demonstrated in this study. With the prominent immune responses from the loss of inhibitory signaling in FcγRIIb-/- mice, HP infection in these mice induced intense chronic inflammation, increased antibody production, and enhanced lupus severity. Thus, the increased systemic inflammatory responses due to localized HP inducing gastritis in some patients with lupus may enhance lupus progression. More studies are needed.
Highlights
Helicobacter pylori (HP), microaerophilic, spiral-shaped gramnegative bacteria, are organisms that can survive in the highly acidic stomach environment, and are known to cause chronic gastric inflammation and cancer (Mahachai et al, 2016)
HP infection has shown a protective effect on the development of lupus in a case control study, especially among African-American patients, the relationship of lupus-HP is still intriguing (Sawalha et al, 2004; Hasni et al, 2011)
Despite the case-control study in that report, it is still unclear if the immune response of patients with lupus prone genes is effective against HP or HP infection is protective for lupus
Summary
Helicobacter pylori (HP), microaerophilic, spiral-shaped gramnegative bacteria, are organisms that can survive in the highly acidic stomach environment, and are known to cause chronic gastric inflammation and cancer (Mahachai et al, 2016). HP infection downregulates the expression of Fc gamma receptor IIb (FcγRIIb), the only inhibitory FcγR (Bolland and Ravetch, 2000) on circulating monocyte of patients with autoimmune diseases (Asahi et al, 2008; Wu et al, 2012). As Fcγ receptors (FcγR) is the immunoglobulin superfamily that contributes to the protective functions, in part, by inducing phagocytosis of opsonized microbes, loss of the inhibitory FcγR results in effective organism control but enhances the risk of autoimmune diseases (Ravetch and Bolland, 2001). HP infection has shown a protective effect on the development of lupus in a case control study, especially among African-American patients, the relationship of lupus-HP is still intriguing (Sawalha et al, 2004; Hasni et al, 2011)
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