Virulent or avirulent (dhfr-ts−)Leishmania majorelicit predominantly a type-1 cytokine response by human cellsin vitro

Brodskyn, Cláudia; Beverley, Stephen M.; Titus, Richard G.

doi:10.1046/j.1365-2249.2000.01122.x

Cited by 21 publications

(20 citation statements)

References 24 publications

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“…Predominant development of Th1 or Th0 responses has been observed in these studies (9,30), which probably reflects the great predominance of these responses in humans. The importance of IL-12 has also been confirmed for both species of Leishmania (9,31). An open question is the relationship of such in vitro systems with human cells to in vivo responses in humans.…”

supporting

confidence: 51%

“…In vitro sensitization to Leishmania was performed by using the protocol described by Brodskyn et al (9), with some modifications. Briefly, PBMC were obtained by using a FicollHypaque gradient (Sigma Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…Shankar and Titus (32) developed an in vitro system using cells from lymphoid tissues of naive mice and Leishmania major promastigotes, which reproduced in vivo responses in murine leishmaniasis. In vitro systems for priming human naive cells against Leishmania have been developed for both Leishmania amazonensis (30,31) and L. major (9,19). Predominant development of Th1 or Th0 responses has been observed in these studies (9,30), which probably reflects the great predominance of these responses in humans.…”

mentioning

confidence: 99%

“…In vitro systems for priming human naive cells against Leishmania have been developed for both Leishmania amazonensis (30,31) and L. major (9,19). Predominant development of Th1 or Th0 responses has been observed in these studies (9,30), which probably reflects the great predominance of these responses in humans. The importance of IL-12 has also been confirmed for both species of Leishmania (9,31).…”

mentioning

confidence: 99%

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Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response toLeishmania amazonensisin Healthy Volunteers

et al. 2001

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The initial encounter of Leishmania cells and cells from the immune system is fundamentally important in the outcome of infection and determines disease development or resistance. We evaluated the anti-Leishmania amazonensis response of naive volunteers by using an in vitro priming (IVP) system and comparing the responses following in vivo vaccination against the same parasite. In vitro stimulation allowed us to distinguish two groups of individuals, those who produced small amounts of gamma interferon (IFN-γ) (n = 16) (low producers) and those who produced large amounts of this cytokine (n = 16) (high producers). IFN-γ production was proportional to tumor necrosis factor alpha and interleukin 10 (IL-10) levels but did not correlate with IL-5 production. Volunteers who produced small amounts of IFN-γ in vitro remained low producers 40 days after vaccination, whereas high producers exhibited increased IFN-γ production. However, 6 months after vaccination, all individuals tested produced similarly high levels of IFN-γ upon stimulation of their peripheral blood mononuclear cells with Leishmania promastigotes, indicating that low in vitro producers respond slowly in vivo to vaccination. In high IFN-γ producers there was an increased frequency of activated CD8+ T cells both in vitro and in vivo compared to the frequency in low producers, and such cells were positive for IFN-γ as determined by intracellular staining. Such findings suggest that IVP responses can be used to predict the pace of postvaccination responses of test volunteers. Although all vaccinated individuals eventually have a potent anti-Leishmania cell-mediated immunity (CMI) response, a delay in mounting the CMI response may influence resistance against leishmaniasis

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supporting

confidence: 51%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response toLeishmania amazonensisin Healthy Volunteers

et al. 2001

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“…We next determined whether this association existed during Leishmania infection. To do so, we took advantage of the in vitro priming system (7,48,49). Priming of PBMCs from healthy volunteers (previously characterized as high IFN-␥ producers) with live parasites led to a significant expansion of TCR V␤12 T cells which, in turn, also expressed IL-2R.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the T-Cell Receptor Vβ Repertoire in the Human Immune Response againstLeishmaniaParasites

Clarêncio

Oliveira

Bomfim³

et al. 2006

Infect Immun

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Isoniazid‐induced control of Mycobacterium tuberculosis by primary human cells requires interleukin‐1 receptor and tumor necrosis factor

et al. 2016

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Proinflammatory cytokines are critical mediators that control Mycobacterium tuberculosis (Mtb) growth during active tuberculosis (ATB). To further inhibit bacterial proliferation in diseased individuals, drug inhibitors of cell wall synthesis such as isoniazid (INH) areemployed. However, whether INH presents an indirect effect on bacterial growth by regulating host cytokines during ATB is not well known. To examine this hypothesis, we used an in vitro human granuloma system generated with primary leukocytes from healthy donors adapted to model ATB. Intense Mtb proliferation in cell cultures was associated with monocyte/macrophage activation and secretion of IL-1β and TNF. Treatment with INH significantly reduced Mtb survival, but altered neither T-cell-mediated Mtb killing, nor production of IL-1β and TNF. However, blockade of both IL-1R1 and TNF signaling rescued INH-induced killing, suggesting synergistic roles of these cytokines in mediating control of Mtb proliferation. Additionally, mycobacterial killing by INH was highly dependent upon drug activation by the pathogen catalase-peroxidase KatG and involved a host PI3K-dependent pathway. Finally, experiments using coinfected (KatG-mutated and H37Rv strains) cells suggested that active INH does not directly enhance host-mediated killing of Mtb. Our results thus indicate that Mtb-stimulated host IL-1 and TNF have potential roles in TB chemotherapy.Keywords: Human r IL-1 r TNF r Isoniazid r Leukocytes r Mycobacterium tuberculosis Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionUpon Mycobacterium tuberculosis (Mtb) exposure, it is estimated that 5-10% of human subjects will develop active tuberculosis Correspondence: Prof. André Báfica e-mail: andre.bafica@ufsc.br (TB) [1], which is characterized by intense pathogen proliferation associated with cellular activation and cell death. Cellular structures known as necrotic granulomas may promote bacterial dissemination and enhance Mtb transmission [2,3]. On the other hand, counter balance is supported by host recognition of Mtb, which induces cytokines such as IL-1β and TNF [4,5], two potent inflammatory mediators that suppress Mtb growth [4,6]. It has C 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2016. 46: 1936-1947 Immunity to infection 1937 been shown that these cytokines regulate intracellular bacterial growth in human macrophages, whether by recruitment of antimicrobial effector molecules [7] or induction of apoptotic cell death [8]. In conjunction with 9], IL-1β, and TNF can provide signals to help differentiation and antigen presentation by macrophages [6,10,11]. Moreover, the adverse outcome of latent TB reactivation observed in clinical trials with anti-TNF therapies, additionally confirmed the essential role of TNF for controlling Mtb growth in humans [12]. In addition to antibiotics, which are major therapeutic tools to promote further suppression of mycobacterial growth [13], host-targeted i...

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Virulent or avirulent (dhfr-ts−)Leishmania majorelicit predominantly a type-1 cytokine response by human cellsin vitro

Cited by 21 publications

References 24 publications

Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response toLeishmania amazonensisin Healthy Volunteers

Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response toLeishmania amazonensisin Healthy Volunteers

Characterization of the T-Cell Receptor Vβ Repertoire in the Human Immune Response againstLeishmaniaParasites

Isoniazid‐induced control of Mycobacterium tuberculosis by primary human cells requires interleukin‐1 receptor and tumor necrosis factor

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