Immune Response During HIV and Tuberculosis Co-infection

Bonecini-Almeida, Maria da Glória; Silva, José Roberto Lapa e; Kritski, Afrânio Lineu; Júnior, I Neves; Morgado, Mariza G.; Nathan, Carl; Ho, John L.

doi:10.1590/s0074-02761998000300023

Cited by 7 publications

(3 citation statements)

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“…31,34 In individuals with LTBI the progressive depletion of CD4+ T-cells caused by HIV activity increases the likelihood of Mtb reactivation and disease. 35 HIV infection has also been shown to negatively impact on TB recurrence and treatment failure. 36,37 It is the underlying cause of the paradoxical reaction 38,39 and presumed to increase the likelihood for developing TB drug resistance.…”

Section: Cytokine Dysregulation Drives Immunopathology During Concurrent Hiv and Mtb Infectionmentioning

confidence: 99%

Correlates for disease progression and prognosis during concurrent HIV/TB infection

Siawaya

Rühwald

Eugen‐Olsen

et al. 2007

International Journal of Infectious Diseases

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Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) are both life-threatening pathogens in their own right, but their synergic effects on the immune system during co-infection markedly enhance their effect on the host. This review focuses on the bidirectional interaction between HIV and Mtb and discusses the relevance of sputum smear examination, CD4+ counts, viral load at baseline and after initiation of anti-retroviral therapy, as well as additional existing and new potential immune correlates of disease progression and prognosis. These markers include beta2-microglobulin, neopterin, tumor necrosis factor receptor II (TNFRII), CD8+/CD38+, soluble urokinase plasminogen activator receptor (suPAR) and CXCL10 (or IP-10).

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Section: Cytokine Dysregulation Drives Immunopathology During Concurrent Hiv and Mtb Infectionmentioning

confidence: 99%

Correlates for disease progression and prognosis during concurrent HIV/TB infection

Siawaya

Rühwald

Eugen‐Olsen

et al. 2007

International Journal of Infectious Diseases

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“…We hypothesize that the deactivating cytokines are responsible for this hindrance. In a subsequent study, we assessed the quantity of cytokines present in the bronchoalveolar lavage fluid of TB patients (5) . We determined that levels of the cytokine that activates macrophage microbicidal function, namely IFN-γ , are increased, as we want them to be.…”

Section: The Role Of Cytokines In the Development Of Tuberculosismentioning

confidence: 99%

O ressurgimento da tuberculose e o impacto do estudo da imunopatogenia pulmonar

Silva

Boéchat

2004

J. bras. pneumol.

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O ressurgimento da tuberculose como uma das doenças contagiosas que mais assola a humanidade deu-se após uma falsa impressão de que se caminhava para o seu controle antes do final do Século XX. Nos últimos dez anos, em associação com centros de pesquisas norte-americanos e europeus, nosso grupo na Universidade Federal do Rio de Janeiro tem estudado diversos aspectos relacionados com a patogenia da forma pulmonar, a mais importante por conta de sua freqüência e importância que tem no ciclo de transmissão. Nossa hipótese é que o estabelecimento da infecção latente e o desenvolvimento da forma ativa dependem de um desequilíbrio entre citocinas ativadoras e desativadoras da função microbicida dos macrófagos. A despeito da presença de mecanismos habitualmente protetores, como de moléculas nos macrófagos que denotam ativação celular e de moléculas comprometidas com a proteção contra a tuberculose, como o óxido nítrico e o interferon-g, a tuberculose progride. Um dos motivos é a presença no sítio de infecção de moléculas como a interleucina-10 e o TGF-b, que tem capacidade de desativar macrófagos previamente ativados. Existem evidências que a micobactéria secreta proteínas capazes de induzir a expressão de interleucina-10, agindo assim para burlar os mecanismos de defesa. Indivíduos suscetíveis teriam mais capacidade de responder a estas moléculas da micobactéria, devido a mutações genéticas que facilitam a produção de interleucina-10. A compreensão destes mecanismos poderá representar avanços na prevenção e descoberta de novos alvos terapêuticos para o controle da tuberculose.

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“…Indeed, IFN-γ induced classical macrophage activation appears to be essential for mycobacterial killing through the induction of nitric oxide production and related reactive nitrogen intermediates (RNI) by macrophages through the action of inducible nitric oxide synthase (iNOS) [14]. In contrast, helminth infection-generated IL-4 induced, arginase (ARG-1) expressing alternative macrophage activation has been shown in murine systems to lead to impaired mycobacterial immunity [15].…”

Section: Introductionmentioning

confidence: 99%

Mycobacteria induce TPL-2 mediated IL-10 in IL-4-generated alternatively activated macrophages

et al. 2017

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IL-4 drives expansion of Th2 cells that cause generation of alternatively activated macrophages (AAMs). Filarial infections are established early in life, induce increased IL-4 production are co-endemic with tuberculosis (TB). We sought to understand, therefore, how mycobacteria are handled in the context of IL-4-induced AAM. Comparing IL-4 generated in vitro monocyte derived human AAMs to LPS and IFN-γ generated classically macrophages (CAMs), both infected with mycobacteria (BCG), we demonstrated increased early BCG uptake and increased IL-10 production in AAMs compared to CAMs. We further demonstrated that increased IL-10 production is mediated by upregulation of tumor progression locus 2 (TPL-2), an upstream activator of extracellular signal related kinases (ERKs) in AAMs but not in CAMs, both at the transcript as well as the protein level. Pharmacologic inhibition of TPL-2 significantly diminished IL-10 production only in BCG-infected AAMs. Finally, we validated our findings in an in vivo C57Bl/6 model of filarial infection, where an exaggerated Th2 induced lung-specific alternative activation led to TPL-2 and IL-10 upregulation on subsequent TB infection. These data show that in response to mycobacterial infection, IL-4 generated AAMs in chronic filarial infections have impaired immune responses to TB infection by increasing IL-10 production in a TPL-2 mediated manner.

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Immune Response During HIV and Tuberculosis Co-infection

Cited by 7 publications

References 0 publications

Correlates for disease progression and prognosis during concurrent HIV/TB infection

Correlates for disease progression and prognosis during concurrent HIV/TB infection

O ressurgimento da tuberculose e o impacto do estudo da imunopatogenia pulmonar

Mycobacteria induce TPL-2 mediated IL-10 in IL-4-generated alternatively activated macrophages

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