Author Report for: Islas-Weinstein L

INTRODUCTION: Tuberculosis (TB) is the first cause of mortality by a single infectious agent in the world, causing more than one million deaths worldwide as reported by the World Health Organization (WHO). For the optimal control of TB infection, a protective immune response that limits bacterial spread without causing damage to the host is essential. Although most healthy individuals are capable of generating protective responses, patients who suffer pulmonary TB commonly present a defective immune function. Areas covered: We intend to highlight the potential of novel immunotherapeutic strategies that enhance and promote effective immune responses. The following methodology was undertaken for establishing a literature search: the authors used PubMed to search for 'Pulmonary Tuberculosis' and keywords that denoted the novel immunotherapeutic strategies discussed in length in the text including antibodies, antimicrobial peptides, cell therapy, cytokines and gene therapy. Expert commentary: The current therapeutic regimens for this disease are complex and involve the prolonged use of multiple antibiotics with diverse side effects that lead to therapeutic failure and bacterial resistance. The standard appliance of immunotherapy and its deployment to vulnerable populations will require coordinated work and may serve as a powerful tool to combat the ensuing threat of TB.

Acetylcholine is an endogenous alpha4beta2 and alpha7 nicotinic receptor agonist that is basally secreted in the lungs of mammals. Agonism of these receptors has been associated with an increased Th2 immune response, decreased Th1 and Th17 immune responses. Using high performance liquid chromatography, lungs of BALB/c mice infected with Mycobacterium tuberculosis (Mtb.) H37Rv, revealed an increased level of acetylcholine expression in lung two weeks and two months after infection. These elevations may be associated with immunopathological progression of the disease (inefficient granuloma formation, increased lung pneumonia and bacillary burdens). Mice therefore received saline solution (control group), and either receptor selective antagonist: alpha4beta2 nicotinic or alpha7 nicotinic during both periods of acetylcholine exacerbation. Mice lungs were obtained after treatment of each group and Mtb colony-forming units (CFUs) and morphometric analysis were realized. Administration of nicotinic receptor antagonists resulted in larger granulomas and lower pneumonic areas and CFUs when compared with the control group. The cholinergic system may hence emerge as a novel therapeutic target in treating TB infection, improving the host's response during the disease.

Recent studies suggest that catecholamines (CAs) and acetylcholine (ACh) play essential roles in the crosstalk between microbes and the immune system. Host cholinergic afferent fibers sense pathogen-associated molecular patterns and trigger efferent cholinergic and catecholaminergic pathways that alter immune cell proliferation, differentiation, and cytokine production. On the other hand, microbes have the ability to produce and degrade ACh and also regulate autogenous functions in response to CAs. Understanding the role played by these neurotransmitters in host-microbe interactions may provide valuable information for the development of novel therapies.