1.Dendritic cell TLR4 induces Th1-type immune response against Cryptosporidium parvum infection
Xu, Q.M. ; Fang, F. ; Wu, S.H. ; Shi, Z.Q. ; Liu, Z. ; Zhao, Y.J. ; Zheng, H.W. ; Lu, G.X. ; Kong, H.R. ; Wang, G.J. ; Ai, L. ; Chen, M.X. ; Chen, J.X.
Tropical Biomedicine 2021;38(No.1):172-179
The objective of this study was to investigate the mechanism of Toll-like receptor (TLR4)-
mediated dendritic cell (DC) immune against Cryptosporidium parvum infection. C. parvum
sporozoites were labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester. Murine
bone marrow-derived DCs were isolated, and divided into TLR4 antibody blocking (TAB;
infected with 2 × 105 labeled sporozoites and 0.5 μg TLR4 blocking antibody), TLR4 antibody
unblocking (TAU; infected with 2 × 105 labeled sporozoites), and blank control (BC; with 1.5
mL Roswell Park Memorial Institute 1640 medium) groups. The adhesion of Cryptosporidium
sporozoites to DCs and CD11c+ levels were examined by fluorescence microscopy and flow
cytometry. Male KM mice were orally injected with C. parvum. The proliferation of T lymphocytes
in spleen, expression of cytokines in peripheral blood, and TLR4 distribution features in
different organs were further determined by immunohistochemistry. A significantly higher
expression of CD11c+ and higher C. parvum sporozoite adhesion were found in the TAU group
compared with other groups. The expression of CD4+CD8-
/CD8+CD4- in the spleen were
obviously differences between the TAB and TAU groups. The expression of TLR4, interleukin
IL-4, IL-12, IL-18 and IFN-γ improved in the TAU group compared with TAB group. Higher
expression of TLR4 was detected in the lymph nodes of mice in the TAU group, with pathological
changes in the small intestine. Hence, TLR4 could mediate DCs to recognize C. parvum,
inducing Th1 immune reaction to control C. parvum infection.