Table 3.

Evidence for a role of host-derived RNI in control of tuberculosis

Evidence	Ref.
In vitro and in mice
Sensitivity of mycobacteria to RNIin vitro	42, 43, 93, 94
Expression of NOS2 at sites of disease in immunocompetent mice	45, 95–99
Lack of NOS2 in immunocompromised mice with progressive disease: malnutrition; knock-outs of β2-microglobulin, T cell receptors, interferon-γ or its receptor, TNF receptor 1	95–99
Exacerbation of infection in macrophages with NOS inhibitors	100–102
Exacerbation of disease in vivo with NOS inhibitors	45, 103, 104
Exacerbation of disease in mice with disrupted NOS2 alleles	45
In human cells
Expression of NOS2 in macrophages from lungs of patients with tuberculosis	46, 47
Production of potentially mycobactericidal amounts of RNI by macrophages from lungs of patients with TB	47
Production of RNI by M. tuberculosis-infected macrophages from lungs of normal donors	48
Production of RNI by M. tuberculosis-infected blood mononuclear cells from both normal and tuberculous donors	105
Killing of mycobacteria by pulmonary macrophages only if they express NOS2, and prevention of killing with a NOS inhibitor	41