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The role of the endocrine system on the immune response, especially in the lung, remains poorly understood. Hormones play a crucial role in the development, homeostasis, metabolism, and response to the environment of cells and tissues. Major infectious and metabolic diseases, such as tuberculosis and diabetes, continue to converge, necessitating the development of a clearer understanding of the immune and endocrine interactions that occur in the lung. Research in bacterial respiratory infections is at a critical point, where the limitations in identifying and developing antibiotics is becoming more profound. Hormone receptors on alveolar and immune cells may provide a plethora of targets for host-directed therapy. This review discusses the interactions between the immune and endocrine systems in the lung. We describe hormone receptors currently identified in the lungs, focusing on the effect hormones have on the pulmonary immune response. Altered endocrine responses in the lung affect the balance between pro- and anti-inflammatory immune responses and play a role in the response to infection in the lung. While some hormones, such as leptin, resistin and lipocalin-2 promote pro-inflammatory responses and immune cell infiltration, others including adiponectin and ghrelin reduce inflammation and promote anti-inflammatory cell responses. Furthermore, type 2 diabetes as a major endocrine disease presents with altered immune responses leading to susceptibility to lung infections, such as tuberculosis. A better understanding of these interactions will expand our knowledge of the mechanisms at play in susceptibility to infectious diseases and may reveal opportunities for the development of host-directed therapies.

Mycobacterium bovis has the largest host range of the Mycobacterium tuberculosis complex and infects domestic animal species, wildlife, and humans. The presence of global wildlife maintenance hosts complicates bovine tuberculosis (bTB) control efforts and further threatens livestock and wildlife-related industries. Thus, it is imperative that early and accurate detection of M. bovis in all affected animal species is achieved. Further, an improved understanding of the complex species-specific host immune responses to M. bovis could enable the development of diagnostic tests that not only identify infected animals but distinguish between infection and active disease. The primary bTB screening standard worldwide remains the tuberculin skin test (TST) that presents several test performance and logistical limitations. Hence additional tests are used, most commonly an interferon-gamma (IFN-γ) release assay (IGRA) that, similar to the TST, measures a cell-mediated immune (CMI) response to M. bovis. There are various cytokines and chemokines, in addition to IFN-γ, involved in the CMI component of host adaptive immunity. Due to the dominance of CMI-based responses to mycobacterial infection, cytokine and chemokine biomarkers have become a focus for diagnostic tests in livestock and wildlife. Therefore, this review describes the current understanding of host immune responses to M. bovis as it pertains to the development of diagnostic tools using CMI-based biomarkers in both gene expression and protein release assays, and their limitations. Although the study of CMI biomarkers has advanced fundamental understanding of the complex host-M. bovis interplay and bTB progression, resulting in development of several promising diagnostic assays, most of this research remains limited to cattle. Considering differences in host susceptibility, transmission and immune responses, and the wide variety of M. bovis-affected animal species, knowledge gaps continue to pose some of the biggest challenges to the improvement of M. bovis and bTB diagnosis.