Table 2.

Heterogeneity of granulomas and other TB lesions.

Heterogeneity characteristic	Examples
Morphology	Lesions can be necrotic, caseous, fibrocaseous, non-necrotizing, neutrophil rich, mineralized, completely fibrotic, or cavitary (7, 138).
Cellular composition	Typically macrophages as well as CD4 and CD8 T cells surrounding a necrotic core, but there can also be multinucleated giant cells, neutrophils, dendritic cells, and fibroblasts (4, 138).
Immune cell response	Early forming granulomas demonstrate type-2 immune response whereas later forming granulomas demonstrate adaptive TH1, TH17 and cytotoxic T cell responses (227). Huge variability in numbers and phenotypes of T cells, and range of cytokine profiles and bacterial burdens (138, 234).
Inflammation	Proper balance of pro/anti-inflammatory responses is needed to control Mtb infection. A more pro-inflammatory response can lead to liquefaction or softening of the caseum (235). A more anti-inflammatory response tends to be associated with an overall better outcome in terms of reactivation as well as long-term prognosis (232). Various inflammatory signatures and killing potentials can be found even within the same granuloma (138, 226, 236). Limitations in the interpretation of these findings include: (i) inability to follow the inflammatory phenotype and correlate with culturable Mtb in single lesions over time and (ii) incapacity to determine whether the inflammation type observed is the cause or effect of the ability or inability of the host to control the infection.