The immunopathogenesis of the HIV tuberculosis immune reconstitution inflammatory syndrome

Abstract

HIV-1 patients co-infected with some pathogens are at risk of developing the immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral therapy (ART). IRIS is characterized by inflammation leading to the clinical worsening of a treated infection or the unmasking of a previously undiagnosed condition or infection. It is commonly associated with tuberculosis (TB), 8-43% of the HIV-TB co-infected patients prescribed with antitubercular treatment and ART develop TB-IRIS. Although IRIS hasbeen recognized for over 20 years, relatively little was known until recently about its pathogenesis. Despite these advances in understanding IRIS, there remains no immune biomarker for diagnostic or prognostic purposes. Here, we review the risk factors associated with TB-IRIS, the challenges in studying this syndrome, and how T lymphocytes, dysregulated cytokine responses, and innate immunity may contribute to the development of TB-IRIS.Keywords: Drug therapy complications r HIV-1 infection r Immune reconstitution inflammatory syndrome r Tuberculosis The association between tuberculosis (TB) and TB-human immunodeficiency virus (TB-HIV)Approximately one third of the world's population is considered latently infected by tuberculosis (TB), of which an estimated 5-10% will develop active disease [1]. TB is a leading infectious cause of adult mortality and morbidity worldwide, second only to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) [2]. In 2011, there were an estimated 8.7 million new cases of TB and 1.4 million deaths [3]. While India Correspondence: Dr. Robert J. Wilkinson e-mail: r.j.wilkinson@imperial.ac.uk and China accounted for almost 40% of the world's TB cases, the African region has the highest incidence and TB-related mortality per capita, attributed mainly to the high prevalence of HIV-1 infection. Among people who are latently infected with TB, HIV-1 is the most important risk factor for developing active TB disease due to progressive immunocompromise. Of the 11 million who were estimated to be dually infected with TB and HIV-1, 79% resided in Africa [3].Several interventions have been implemented to control the TB-HIV-1 syndemic. These include routine HIV testing of TB patients, increased coverage of antiretroviral therapy (ART), intensified TB case finding, and isoniazid preventive therapy for HIV-1-infected persons [3]. The increased accessibility to ART in resource-limited regions has significantly improved the clinical outcome of HIV-1-infected patients and reduced the TB risk by 58-80% [4]. ART can effectively suppress HIV-1 replication, resultingwww.eji-journal.eu 1996 Rachel P. J. Lai et al. Eur. J. Immunol. 2013. 43: 1995 in reduced viral load and increased CD4 + T-cell counts within the first month [5]. The process of CD4 + T-cell recovery begins with the rapid redistribution of the CD45RO + memory population from the lymphoid tissues into the plasma, followed by the slower replenishment of the CD45RA + naïve cells produced in the thymus [5]. This rapid re...

Anti-CD20 Antibody Therapy and Susceptibility to Pneumocystis Pneumonia

“…This suppression leads to an expedient reconstitution of CD4 ϩ T cells, which then react to an accumulation of viable infections and/or residual microbial antigens acquired during immunosuppression. As a result, the host can experience a massive amount of inflammation in multiple organs, primarily the lungs and central nervous system (CNS) (30,31). This immunopathology is mediated through CD4 ϩ T cells (32), but it was previously shown that other cell types, such as CD8 cells, modulate the pathology by increasing the T reg :T effector ratio (33).…”

Neutrophil Activation and Enhanced Release of Granule Products in HIV-TB Immune Reconstitution Inflammatory Syndrome: Erratum

“…26,27 However, TB-IRIS is not explained simply by a change in CD4 numbers, and innate cells are also implicated in the syndrome. 5,12 Neutrophils are increasingly recognized in TB pathology, 28-30 as we have described in TB-meningitis IRIS, 6 but they had not previously been studied in this detail.…”

“…3 TB-IRIS has been associated with perturbations in both the adaptive and innate immune systems. 4,5 These include increased secretion of neutrophil-associated mediators such as S100A8/A9 and matrix metalloproteinases, [6][7][8] perforin and granzyme B by CD4 + T cells, 9 higher expression and imbalance of C1Q and C1-inhibitor (complement system), 10 activation of monocytes, 11 inflammasome and Toll-like receptor signaling 12,13 , as well as elevated chemokine and cytokine production [14][15][16] with a particular role for the IL-10 family. 17 Although rapid changes in CD4 + T-cell count have long been associated with all forms of IRIS, recent research has focused on these latter phenomena of inflammasome activation and release of soluble mediators from innate cells.…”

L’iris

“…On estime que jusqu'à un tiers de la population mondiale est infectée de façon latente par Mtb, et que 5 à 10 % des personnes infectées évoluent vers une tuberculose active [2]. La co-infection par le VIH augmente considérablement la probabilité de réactivation et la sévérité de la tuberculose.…”