[Animal Modeling]-Blocking the PD1/PD-L1 pathway mediated by macrophages inhibits the recurrence of tuberculosis in mice

  Purpose: Functional PD? Using L1 (programmed cell death ligand 1, PD 2 L1) monoclonal antibody, PD1/PD 3. To study the mechanism of immune intervention and relapse after tuberculosis treatment by blocking the L1 pathway.

  Method: C57BL/6 female mice were infected with 106CFUH37Rv through the tail vein and developed acute tuberculosis infection. After 2 weeks, PD isoniazid (10 mg/kg) and isoniazid? Combined with L1 monoclonal antibody (50μg each time) for continuous administration. After 4 weeks of treatment, a latent infection was obtained. During the incubation period, TNFα antibody (50 μg each) was used to induce recurrence for 4 weeks. By quantitatively analyzing the histopathology and bacterial load of the lung, spleen and liver at each time point to study PDL1: Intervention effect of monoclonal antibodies on active tuberculosis and tuberculosis recurrence in mice? Can in vitro experiments be used to further clarify the effect of PD knockout? Can L1 resist the apoptosis of macrophages infected by tuberculosis?

  Result: After infection of mice, the first two peripheral lungs, spleen and liver have a higher bacterial load (3-4LgCFU/mL), granulomatous disease is more serious, manifested as active tuberculosis. Isoniazid, Isoniazid and PD? After 4 weeks of treatment with the L1 monoclonal antibody combination, the counts of lung, spleen and liver bacteria were significantly lower than the model control group, and the granulomatous lesions were also significantly reduced, but there was no significant difference between the two treatment groups. During the relapse period, compared with isoniazid treatment, the isoniazid and PDL1 monoclonal antibody treatment group can be combined into the treatment group to significantly reduce the bacterial load in the relapsed tissue and reduce pathological changes. In vitro experiments have confirmed that PD L1 antibody or siRNA is used to knock out PD L1 in macrophages, and both can promote the apoptosis of macrophages infected by tuberculosis.