Table 6.

Similarities and differences between the immunopathological changes in the tracheal mucosa induced by M. gallisepticum in mature birds and young birds (28).

Feature		References
Similarities
(1) Robust inflammatory response mediated by cytokines, chemokines and TLRs.
	Up-regulation of genes for IL-22, CXCL13, CXCL13-like 2, lymphotactin, CCL-19, CCL-26, IFN-γ, chemokine ah221, MIP-1β, IL-16, CXCL13-like 3, CXCL12 (Table 3).	(46–47, 48)
	Up-regulation of genes for TLR7, TLR1 family member A and TLR2 family member B (Table 3).	(26, 27, 47)
	Enrichment of GOs (Figures S2-3), pathways (Figure 3) and protein classes (Table 4) involved in cytokine/chemokine production, signaling and receptor binding.
(2) Ability of M. gallisepticum to induce local activation and proliferation of inflammatory cells increasing the mucosal thickness.
	Up-regulation of genes and enrichment of GOs (Figures S1-3), pathways (Figure 3) and protein classes (Table 4) involved in DNA replication and cell cycle.
(3) Ability of M. gallisepticum to suppress TLR5-mediated responses against flagellated bacteria.
	Down-regulation of TLR5 (Table 3)	(49)
(4) B cell migration and onset of adaptive immune response 2 weeks after infection following a phase of immune dysregulation.
	Up-regulation of genes for B cell chemoattractants including CXCL13, CXCL13-like 2, CXCL13-like 3, lymphotactin and IL-16 (Table 3).	(50)
	Increased CXCL12-CXCR4 interaction (Table 3).	(51)
	Enrichment of GOs involved in B cell recruitment (Figure S3).
(5) Macrophage driven phagocytosis
	Up-regulation of genes for IFN-γ, MIP-1β, and chemokine ah221 (Table 3)
	Enrichment of GOs (Figure S3) involved in phagocytosis
	Enrichment of pathways involved in phagocytosis including Activation of formins and NADP oxidase by Rho GTPases (Figure 3)
(6) Impaired formation and motor movement of cilia
	Down-regulation of genes (Table 2) and enrichment of GOs (Figures S4-6), pathways (Figure 4) and protein classes (Table 4) with down-regulated genes involved in formation and motor movement of cilia, with more effect on anterograde intraflagellar transport mediated by dynein arm	(25, 52–54)
(7) Impaired formation of cellular cytoskeleton
	Down-regulation of genes (Table 2) and enrichment of GOs (Figures S4-6), pathways (Figure 4) and protein classes (Table 4) with down-regulated genes involved in formation of cytoskeleton
Differences
(1) Decreased severity of inflammation
	No significant difference in transcription of genes for IL-17A, IL-1β, IL-6, and IL-8, which are known proinflammatory cytokines	(55, 56)
	No significant difference in the transcription of IL-1 receptor 2, which acts as a “decoy receptor” for IL-1β, decreasing the effective level of IL-1β	(57)
	Enrichment of PD-1 signaling pathway (Figure 2) with up-regulated genes. PD-1 signaling pathway reduces inflammation by immunosuppression through inhibition of T cell proliferation, cytokine production and cytolytic function	(58)
(2) No damage to formation of apical intercellular junctional complexes