Effects Of Heligmosomides Polygyrus Infection On Intestinal Mucosal Immune Function In Mice Under Hypoxic Conditions At High Altitude

Objective:It aims to study the effect and mechanism of Heligmosomides polygyrus?H.p.?infection on intestinal mucosal immune function in mice among high altitude hypoxic environment.Methods:Randomly divided 40 female BALB/c mice fed in IVC at 2260 m altitude?Xining,Qinghai,582 mmHg atmospheric pressure,PO₂ 121.6 mmHg,equivalent to16%O₂ at sea level?into four groups:normoxic control group?NC?,normoxic infection group?NI?,hypoxic control group?HC?and hypoxic infection group?HI?.Fed the normoxic group in Xining for 14 days,fed the hypoxic group in a hypobaric oxygen chamber at simulated altitude of 5000 m?405 mmHg atmospheric pressure,PO₂ 84.7 mmHg,equivalent to 11%O₂ at sea level?for 14 days,and infected the infection group with 200 larvae in H.p.L3 stage by intragastric administration.After14 days,the body weight and colon histomorphology of mice in four groups were observed,the length of mice small intestine was measured,the number of H.p.in the infected group was counted,the contents of IL-4,IL-10,IL-17,IFN-?in the T lymphocyte culture medium supernatant of spleen and mesenteric lymph nodes and IgE,IgG1 and IgG2a in serum were detected by ELISA,and the expressions of IL-4,IL-10,IL-17 and IFN-?in small intestine were detected by quantitative PCR.Results:?1?Compared with the non-infection group,the duodenum of mice in each infection group was markedly hyperemic,dilated and parasitic with a large number of H.p.nematodes.?2?Compared with NC group,the weight of mice in HC group decreased significantly?P<0.05?,the length of small intestine increased significantly?P<0.05?,the IgE antibody content in serum increased significantly?P<0.05?,and the IgG2a and IgG1 antibody content decreased with no statistical difference;the content of IL-4 secreted by splenic T lymphocyte was not significantly changed?P>0.05?,but the contents of IL-10,IL-17 and IFN-?were significantly decreased?P<0.05?;the content of IL-4 and IL-17 secreted by T lymphocyte in mesenteric lymph nodes was not significantly changed?P>0.05?,but the contents of IL-10 and IFN-?were significantly decreased?P<0.05?;the expression of IL-4,IFN-?and IL-17 in duodenum did not change significantly,but the content of IL-10 decreased significantly?P<0.05?;the weight of mice in NI group did not decrease significantly,the length of small intestine increased significantly?P<0.05?,IgG1 and IgE antibodies in serum increased significantly?P<0.05?,and IgG2a antibodies decreased significantly?P<0.05?;the content of IL-4and IL-10 secreted by T lymphocytes in mesenteric lymph nodes and spleens of mice increased significantly?P<0.05?,while the content of IFN-?and IL-17 decreased significantly?P<0.05?;the expression of IL-4 and IL-10 in duodenum increased significantly?P<0.05?,while the expression of IFN-?and IL-17 decreased significantly?P<0.05?.?3?Compared with HC group,the weight of mice in HI group did not decrease significantly,the length of small intestine increased significantly?P<0.05?,the serum IgG1 and IgE antibodies increased significantly?P<0.05?,IgG2a antibodies decreased significantly?P<0.05?;the content of IL-4and IL-10 secreted by T lymphocytes in mesenteric lymph nodes and spleens increased significantly?P<0.05?,IFN-?and IL-17 decreased significantly?P<0.05?,and the expressions of IL-4 and IL-10 in duodenum increased significantly?P<0.05?,while the expressions of IFN-?and IL-17 decreased significantly?P<0.05?.?4?Compared with NI group,the weight of mice in HI group decreased significantly?P<0.05?,the length of small intestine increased insignificantly?P>0.05?,and the number of parasites parasitized in duodenum increased significantly?P<0.05?;IgE and IgG2a antibodies in serum increased significantly?P<0.05?,while IgG1antibodies did not change significantly;the content of IL-4,IFN-?,IL-10 and IL-17secreted by T lymphocytes in spleens and mesenteric lymph nodes decreased significantly?P<0.05?;the expression of IL-4 and IL-17 in duodenum decreased significantly?P<0.05?,while the expression of IFN-?and IL-10 decreased with no significant difference.Conclusion:Heligmosomoides polygyrus infection can induce the Th0differentiation toward Th2 and Treg,mediate the humoral immune response and increase the secretion of IL-4,IgE and other immune related factors and antibodies,at the same time,Heligmosomoides polygyrus infection can also inhibit the Th0differentiation toward Th1 and Th17 and decrease the cellular immune response.Hypoxia can inhibit the immune response of intestinal mucosa to the infection of Heligmosomoides polygyrus in mice,and aggravate the pathological damage caused by the infection of Heligmosomoides polygyrus.