Immunological interventions in bacterial infections: From mechanisms to clinical applications

• The article explores the shift from pro-inflammatory to anti-inflammatory immune responses during the progression from acute to chronic bacterial infections with different immunological intervention. • Application of immune checkpoints like PD-1, Tim-3, and TIGIT by the bacteria to evade immune surveillance and promote long-term colonization. • Evaluation of advanced therapeutic strategies including cytokine modulation (TNF-α, TGF-β), passive antibody therapy, cellular immunotherapies, and therapeutic vaccination aimed to restore immune homeostasis. • Different bacteria manipulate macrophage polarization to suppress host immunity and the potential of innate immune boosting to overcome immunosuppression. The rise of multiantibiotic-resistant bacteria poses a major challenge to infection management, as some bacteria survive even antibiotic therapy by evading immune responses. With decreasing treatment options due to increased antibiotic resistance, there is an urgent need for alternative or adjunctive therapies. Immunotherapy, widely used in cancer treatment for its ability to overcome immunosuppression, is emerging as a promising approach for bacterial infections, including persistent and drug-resistant diseases like tuberculosis. Strategies such as immune checkpoint inhibition, cytokine modulation, and cellular therapies are demonstrating potential in preclinical studies. These approaches aim to restore or enhance host immunity against bacterial pathogens. Given the growing threat of resistance, advancing immunotherapy into clinical use requires rigorous trials to validate safety and efficacy. This review discusses the therapeutic promise of immunotherapies against bacterial infections, highlights recent advancements, and outlines current and future directions in the field.