Figure 1.

One possible mechanism that illustrates the immunology of IRIS in a subject with HIV/TB coinfection. Compromised gut immunity leads to increased translocation of luminal gram negative bacterial LPS into the systemic circulation. Initiation of HAART in the subject leads to abrupt restoration of CD4+ T-cells and almost any pathogen-specific immune response. IRIS developers have a high burden of LPS and proinflammatory cytokines produced against LPS could result in an exaggerated, nonspecific attack on latent mycobacterial antigens that are presented in the local lymph nodes leading to localized inflammation. We also hypothesize that subjects that do not develop IRIS could have developed either tolerance (anergy) to persistent LPS and tubercle antigens or could have normal FOXP3+ gene (not shown) and that those with defective FOXP3+ gene or enormous plasma LPS could be vulnerable to IRIS (as demonstrated by researchers that defective FOXP3+ gene is associated with increased risk for inflammatory conditions). (Bold lines indicate the availability of clinical/experimental evidence and dashed lines indicate the possible mechanism).