Cancers are a risk factor for active tuberculosis (TB), and anti-cancer drugs can independently cause TB progression. To understand the underlying mechanisms, mice infected with Mycobacterium tuberculosis (Mtb) were treated with gemcitabine (Gem), cisplatin, or paclitaxel. These treatments delay Mtb-specific T cell responses, increase bacterial loads, and cause hyperinflammation with permissive neutrophils in the lungs. However, depleting Mtb-permissive neutrophils reduce bacterial levels and G-CSF production, thereby attenuating lung immunopathology. Additionally, Mtb-specific T cell responses generated by BCG vaccination inhibit bacterial growth and neutrophil infiltration even after Gem treatment. Gem induce... More
Cancers are a risk factor for active tuberculosis (TB), and anti-cancer drugs can independently cause TB progression. To understand the underlying mechanisms, mice infected with Mycobacterium tuberculosis (Mtb) were treated with gemcitabine (Gem), cisplatin, or paclitaxel. These treatments delay Mtb-specific T cell responses, increase bacterial loads, and cause hyperinflammation with permissive neutrophils in the lungs. However, depleting Mtb-permissive neutrophils reduce bacterial levels and G-CSF production, thereby attenuating lung immunopathology. Additionally, Mtb-specific T cell responses generated by BCG vaccination inhibit bacterial growth and neutrophil infiltration even after Gem treatment. Gem induces granulocyte-biased generation in the bone marrow via G-CSF signaling, which led to lung neutrophil inflammation. However, pre-existing Mtb-specific T cell responses from BCG vaccination normalizes granulopoiesis by restricting G-CSF production. These findings show the mechanism of anti-cancer drug-induced neutrophilic lung inflammation in TB and highlight the role of Mtb-specific T cell responses in maintaining balanced hematopoiesis against Gem-induced TB immunopathogenesis.
