PI3K/AKT/Bcl-2/Bax pathway activation and CD4+ T cell apoptosis induced by Chlamydia muridarum respiratory tract infection

Objective To investigate PI3K/AKT/Bcl-2/Bax pathway activation and CD4+ T cell apoptosis in a mouse model of Chlamydia muridarum (Cm) respiratory tract infection. Methods C57BL/6 mice were infected with 1×103 inclusion forming units (IFUs) of Cm through nasal inhalation. Mononuclear cells were isolated from lung tissues of the infected mice at different points. Expression of PI3K p110δ at mRNA level was detected by RT-PCR. Western blot was used to detect the expression of p-AKT, Bcl-2 and Bax at protein level. Apoptosis of CD4+ T cells in lung tissues of mice was detected by flow cytometry. Results The expression of PI3K p110δ at mRNA level and p-AKT, a downstream protein of PI3K, at protein level in lung tissues of mice with Cm infection were significantly higher than those in non-infected group on day 3, reached to the highest level on day 7 and decreased on day 14. The expression of apoptosis-related proteins Bcl-2 and Bax significantly increased on day 3 and peaked on day 7, while the Bcl-2/BAX ratio decreased following Cm infection. These results suggested that the anti-apoptotic effect gradually decreased and the apoptosis of CD4+ T cells increased. The early apoptosis (Annexin+ PI+ ) and the total apoptosis (Annexin+ PI) of CD4+ T cells induced by Cm infection in lung tissues of mice began to increase on day 3 and peaked on day 7. Conclusion Cm respiratory tract infection induces the activation of PI3K/AKT/Bcl-2/Bax pathway, which results in the apoptosis of CD4+ T cells. Key words: Chlamydia muridarum (Cm); PI3K/AKT; CD4+ T cell; Apoptosis