Immunological mechanisms involved in the protection against development of pulmonary tuberculosis in naturally infected goats

Abstract

Tuberculosis (TB) is a notifiable zoonotic disease caused by bacteria of the Mycobacterium tuberculosis complex (MTC) that affects a multitude of domestic and wild species. The main lesions caused by these mycobacteria are tuberculous granulomas, which determine the organism’s immune response to the disease. Although TB pathogenesis in cattle has been extensively studied, information regarding its progression in other species of interest for the maintenance and transmission of TB such as goats remains limited. This study aimed to characterise the immune response developed in the lungs of goats naturally infected with mycobacteria of MTC by assessing key cell populations and immunomodulatory molecules involved in defending against TB. Hence, twelve 6 to 12-month-old Guadarrama kid goats, initially TB-free, were selected and exposed to M. bovis through close contact with other infected goats. Only animals that tested positive by any of the TB diagnostic methods at the end of the experiment were included in the final analysis (n=9). Gross and microscopic lesions compatible with TB (TBL) in different organs, as well as local response to TB in lungs were evaluated. Our results revealed that after five months of exposure, 44.4% of the M. bovis-infected animals exhibited TBL in the lungs (TBLL+), characterized by a predominance of non-cavitary necrotic granulomas. TBLL+ animals showed significantly higher presence of neutrophils, macrophages (MΦs) and lymphocytes along with greater expression of interferon (IFN)-γ. Conversely, the remaining animals did not present macroscopic or microscopic TBL in the lungs (TBLL-). However, these goats displayed elevated expression of toll-like receptors (TLR)2 and TLR4 alongside heightened expression of pro-inflammatory cytokines, inducible nitric oxide synthase (Inos) and interleukin (IL)-10. These results suggest the potential development of an effective immune response that may suppress or delay of TBL in infected animals. Further research is needed to elucidate how these molecules, which are involved in the defence against MTC, confer protection and modulate their expression during infection for TB control.