Ghosh Nillu, Ghosh Prachetash, Kesh Kousik, Mukhopadhyay Asish K, Swarnakar Snehasikta
Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullik Road, Jadavpur, Kolkata, 700032 India.
National Institute of Cholera and Enteric Diseases, Kolkata, India.
Gut Pathog. 2017 Mar 9;9:14. doi: 10.1186/s13099-017-0161-5. eCollection 2017.
colonize in stomach of ~50% of the world population. pathogenicity Island of is one of the important virulent factors that attributed to gastric inflammation. Coinfection with strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of infection by both strain (SS1) and strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa.
Mice infected with AM1/SS1 strain exhibited less gastric inflammation and reduced proMMP9 and proMMP3 activities in gastric tissues as compared to SS1/SS1 and SS1/AM1 infected groups. The expression of both MMP9 and MMP3 followed similar trend like activity in infected tissues. Both Th1 and Th17 responses were induced by SS1 strain more profoundly than AM1 strain infection which induced solely Th1 response in spleen and gastric tissues. Moreover, IFN-γ, TNF-α, IL-1β and IL-12 were significantly downregulated in mice spleen and gastric tissues infected by AM1/SS1 compared to SS1/SS1 but not with SS1/AM1 coinfection. Surprisingly, IL-17 level was dampened significantly in AM1/SS1 compared to SS1/AM1 coinfected groups. Furthermore, number of Foxp3 T-regulatory (Treg) cells and immunosuppressive cytokines like IL-10 and TGF-β were reduced in AM1/SS1 compared to SS1/SS1 and SS1/AM1 coinfected mice gastric tissues.
These data suggested that prior strain infection attenuated the severity of gastric pathology induced by subsequent strain in C57BL/6 mice. Prior AM1 infection induced Th1 cytokine IFN-γ, which reduced the Th17 response induced by subsequent SS1 infection. The reduced gastritis in AM1/SS1-infected mice might also be due to enrichment of AM1- primed Treg cells in the gastric compartment which inhibit Th1 and Th17 responses to subsequent SS1 infection. In summary, prior infection by non-virulent strain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expression.
在全球约50%的人口胃部定植。幽门螺杆菌的致病岛是导致胃部炎症的重要致病因素之一。不同基因组成的幽门螺杆菌菌株合并感染会改变致病性程度以及对抗生素的敏感性。本研究调查了幽门螺杆菌AM1菌株和SS1菌株感染对宿主的免疫调节作用。将C57BL/6小鼠分别感染AM1菌株或SS1菌株，以及先感染AM1再感染SS1（AM1/SS1），反之亦然。
与SS1/SS1和SS1/AM1感染组相比，感染AM1/SS1菌株的小鼠胃部炎症较轻，胃组织中前MMP9和前MMP3活性降低。MMP9和MMP3在感染组织中的表达趋势与活性相似。SS1菌株诱导的Th1和Th17反应比AM1菌株感染更强烈，AM1菌株感染仅在脾脏和胃组织中诱导Th1反应。此外，与SS1/SS1相比，AM1/SS1感染的小鼠脾脏和胃组织中IFN-γ、TNF-α、IL-1β和IL-12显著下调，但与SS1/AM1合并感染组无差异。令人惊讶的是，与SS1/AM1合并感染组相比，AM1/SS1中IL-17水平显著降低。此外，与SS1/SS1和SS1/AM1合并感染的小鼠胃组织相比，AM1/SS1中Foxp3调节性T（Treg）细胞数量以及IL-10和TGF-β等免疫抑制细胞因子减少。
这些数据表明，先前的幽门螺杆菌菌株感染减轻了C57BL/6小鼠随后感染幽门螺杆菌菌株引起的胃部病理严重程度。先前的AM1感染诱导Th1细胞因子IFN-γ，从而减少了随后SS1感染诱导的Th17反应。AM1/SS1感染小鼠胃炎减轻也可能是由于胃中AM1启动的Treg细胞富集，抑制了对随后SS1感染的Th1和Th17反应。总之，先前非致病性幽门螺杆菌菌株（AM1）感染通过调节炎性细胞因子和MMPs表达，减少了随后致病性菌株（SS1）的感染。
