Modulation of the immune response toMycobacterium tuberculosisduring malaria/M. tuberculosisco-infection

Abstract

A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/cei.12861This article is protected by copyright. All rights reserved. 2 ABSTRACTTuberculosis (TB) causes significant morbidity and mortality on a global scale. The African region has 24% of the world TB cases. TB overlaps with other infectious diseases such as malaria and HIV which are also highly prevalent in the African region. TB is a leading cause of death among HIVpositive patients and co-infection with HIV and TB has been described as a syndemic. In view of the overlapping epidemiology of these diseases, it is important to understand the dynamics of the immune response to TB in the context of co-infection. We investigated the cytokine response to purified protein derivative (PPD) in peripheral blood mononuclear cells from TB patients coinfected with HIV or malaria and compared it to that of malaria-and HIV-free TB patients. A total of 231 subjects were recruited for this study and classified into 6 groups; Untreated TB positive, TB positive subjects on TB drugs, TB and HIV positive, TB and malaria positive, latent TB, and apparently healthy control subjects. Our results demonstrate maintenance of IFN-γ production in HIV and malaria co-infected TB patients in spite of lower CD4 counts in the HIV-infected cohort. Malaria co-infection caused an increase in the production of the Th2-associated cytokine IL-4 and the anti-inflammatory cytokine IL-10 in PPD-stimulated cultures. These results suggest that malaria co-infection diverts immunity response against M. tuberculosis towards a Th-2/antiinflammatory response which might have important consequences for disease progression. Keywords: tuberculosis, HIV, malaria, co-infection, cytokines Page 32 of 52 Clinical Experimental ImmunologyThis article is protected by copyright. All rights reserved.3 Introduction Tuberculosis (TB) is an infectious disease that causes significant morbidity and mortality on a global scale [1]. Pulmonary tuberculosis caused by infection with Mycobacterium tuberculosis is the leading cause of death due to a bacterial pathogen and is responsible for 1.4 million deaths annually [2]. In 2011, there were an estimated 8.7 million new cases of TB and 1.4 million people died from TB, including almost one million deaths among HIV-negative individuals and 430,000 among people who were HIV positive [3]. TB is second only to HIV/AIDS as the biggest killer worldwide due to a single infectious agent [4]. Host immune response...

Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children

“…Although the first published report of malaria TB co-infection was in 1945, (227) there are only few papers published to date, including a case of perinatal malaria and TB in an infant (228), and several epidemiological surveys with prevalence varying from 37% in hospitalized adult and pediatric TB patients in Angola, to 4.3% among adult pulmonary TB patients in Tanzania (229, 230). Co-infections have been studied in both animal models and humans (226, 231–234), and biological interactions seem to exist between P. falciparum, M. tuberculosis , and a shared human host.…”

Tuberculosis and malaria walk side by side in the Brazilian Amazon: an ecological approach

“…To understand the biological interaction between these two pathogens in vivo , infected mice with Mtb and, eight weeks later, with a non‐lethal P. yoelii strain, showed that the co‐infected mice were less able to contain the growth of Mtb in the lung, spleen and liver, thus increasing mortality . These results those of studies that demonstrate activation of TB after malaria exposure – evidence that malaria parasites can suppress host cellular and humoral immune responses during Mycobacterium tuberculosis (Mtb) infection . Disease control strategies for populations for which both diseases are endemic should consider the influence of increased incidence of one infection on the other .…”

Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients

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