Tuberculous Granuloma: Emerging Insights From Proteomics and Metabolomics

Abstract

Mycobacterium tuberculosis infection, which claims hundreds of thousands of lives each year, is typically characterized by the formation of tuberculous granulomas - the histopathological hallmark of tuberculosis (TB). Our knowledge of granulomas, which comprise a biologically diverse body of pro- and anti-inflammatory cells from the host immune responses, is based mainly upon examination of lungs, in both human and animal studies, but little on their counterparts from other organs of the TB patient such as the brain. The biological heterogeneity of TB granulomas has led to their diverse, relatively uncoordinated, categorization, which is summarized here. However, there is a pressing need to elucidate more fully the phenotype of the granulomas from infected patients. Newly emerging studies at the protein (proteomics) and metabolite (metabolomics) levels have the potential to achieve this. In this review we summarize the diverse nature of TB granulomas based upon the literature, and amplify these accounts by reporting on the relatively few, emerging proteomics and metabolomics studies on TB granulomas. Metabolites (for example, trimethylamine-oxide) and proteins (such as the peptide PKAp) associated with TB granulomas, and knowledge of their localizations, help us to understand the resultant phenotype. Nevertheless, more multidisciplinary 'omics studies, especially in human subjects, are required to contribute toward ushering in a new era of understanding of TB granulomas - both at the site of infection, and on a systemic level.

Keywords: adaptive immunity; biomarkers; innate immunity; metabolomics; proteomics; tuberculosis (TB); tuberculous granuloma; tuberculous meningitis.