CD4 and HIV infectious disease: Natural examples are individuals with advanced HIV infection (73, 249) or with genetic defect in IFNγ-IL-12 axis (Medelian Susceptibility to Mycobacterial Diseases) who are vulnerable to systemic mycobacterial infections (250, 253) due to CD4+IFNγ+ deficiency resulting in massive Mtb burden and necrotic macrophage death (Figure 4A). Deficiency of IFNγ may also augment IL-17 production, inducing neutrophil influx (258). Appropriate IFNγ production induces IDO-1 that inhibits excessive IL-17 production, limiting excessive neutrophil influx (91) (Figure 4C).