Innate Immunity to<i>Mycobacterium tuberculosis</i>

Crevel, Reinout van; Ottenhoff, Tom H. M.; Meer, J.W.M. van der

doi:10.1128/cmr.15.2.294-309.2002

Cited by 501 publications

(319 citation statements)

References 254 publications

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“…It has long been recognized that lactoferrin exerts effects on a variety of leukocytes, including macrophages [55][56][57], the main host cell for both BCG and MTB [58,59]. Previous studies demonstrated that lactoferrin is capable of enhancing BCG-infected macrophage production of IL-12:IL-10 ratio [34], thus generating a cytokine environment that is favorable for promotion of T H 1 immunity [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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The current vaccine for tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an attenuated strain of Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG has proven to be effective in children, however, efficacy wanes in adulthood. Lactoferrin, a natural protein with immunomodulatory properties, is a potential adjuvant candidate to enhance efficacy of BCG. These studies define bovine lactoferrin as an enhancer of the BCG vaccine, functioning in part by modulating macrophage ability to present antigen and stimulate T-cells. BCG-infected bone marrow derived macrophages (BMMs) cultured with bovine lactoferrin increased the number of MHC II + expressing cells. Addition of IFN-γ and lactoferrin to BCG-infected BMMs enhanced MHC II expressiona dna increased the ratio of CD86/CD80. Lactoferrin treated BCG-infected BMMs were able to stimulate an increase in IFN-γ production from presensitized CD3 + splenocytes. Together, these results demonstrate that bovine lactoferrin is capable of modulating BCG-infected macrophages to enhance T-cell stimulation through increased surface expression of antigen presentation and costimulatory molecules, which potentially explains the observed in vivo bovine lactoferrin enhancement of BCG vaccine efficacy to protect against virulent MTB infection.

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Section: Discussionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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“…Pathogens such as M. tuberculosis may elicit release of CXCR3-signaling chemokines from tissue macrophages and immature dendritic cells at the site of infection after recognition by TLR4 [37][38][39]. In addition, mycobacterial signaling via TLR2/TLR6 elicits chemokines that attract PMN [40][41][42][43]. PMN, in turn, guarantee both amplified attraction of T cells and focusing of the reaction to the site of infection via their secretion of CXCR3-signaling chemokines.…”

Section: Discussionmentioning

confidence: 99%

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

et al. 2003

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Among the first cells to invade a site of infection, polymorphonuclear neutrophils (PMN) play an important role in the control of numerous infections. While PMN are considered critical for control of acute infections, their role in chronic infections remains less well understood. Here we report that PMN are essential for accurate early granuloma formation during chronic M. tuberculosis infection without influencing mycobacterial growth restriction. The PMNmediated regulation of granuloma formation depended on chemokines signaling through CXCR3, in particular MIG, as indicated by immune histochemical analysis of lung sections from C57BL/6 wild-type and CXCR3 -/-mutant mice and supported by microarray transcriptome analysis. Hence, PMN play a central role in regulating the focal granulomatous response in the lung, and this early granuloma formation can be segregated from long-term protection against pulmonary M. tuberculosis infection.

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“…The control and resolution of the infection involve the activation of macrophages, in which activated T lymphocytes play a crucial role [4]. The release of proinflammatory cytokines such as IL-1b, TNF, IL-12 or IL-18 from monocytes and monocyte-derived macrophages induces the production of T-cell-derived cytokines, most importantly IFN-g, which in turn will activate macrophages for the killing and elimination of the microorganisms [5,6].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and inflammasome‐mediated pathways for the induction of IL‐1β production by Mycobacterium tuberculosis

et al. 2009

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Proinflammatory cytokines of the IL-1 family play an important role for the anti-mycobacterial host defense mechanisms. In the present study we have deciphered the pathways leading from recognition of Mycobacterium tuberculosis to the production and release of IL-1b, the most important member of the IL-1 family. By stimulating cells defective in various pattern recognition receptors, we could demonstrate that IL-1b production is induced by M. tuberculosis through pathways involving TLR2/TLR6 and NOD2 receptors. In contrast, TLR4, TLR9 and TLR1 receptors are not involved in IL-1b induction. Recognition of M. tuberculosis by TLR and NOD2 leads to transcription of proIL-1b through mechanisms involving ERK, p38 and Rip2, but not JNK. Interestingly, although caspase-1 is necessary for the processing of proIL-1b, activation of caspase-1 is not dependent on the stimulation of cells by M. tuberculosis. Monocytes expressed constitutively active caspase-1. The secretion of IL-1b is dependent on the activation of P2X7-induced pathways by endogenously released ATP. In conclusion, we have dissected the molecular mechanisms responsible for IL-1b production by M. tuberculosis, and that may contribute to a deeper knowledge of the mechanisms of cell activation by M. tuberculosis.Key words: Cytokines . Infections -bacterial . Inflammation IntroductionIt is estimated that approximately one-third of the world population is infected with Mycobacterium tuberculosis, the agent causing tuberculosis (TB), although only 5% of these individuals will eventually develop clinical disease. The WHO estimated that 1.6 million deaths resulted from TB in 2005, equaling 4400 deaths a day [1]. The highest rates of infection and especially the mortality are seen in the developing countries, and rates continue to climb in countries where the prevalence of HIV infection is high, despite the implementation of TB control programs [2]. Furthermore, the increased prevalence of multidrug-resistant strains of M. tuberculosis represents a challenge for treatment programmes [3]. 10.1002/eji.200839115 Eur. J. Immunol. 2009Immunol. . 39: 1914Immunol. -1922 Johanneke Kleinnijenhuis et al. 1914The first line of defense against M. tuberculosis is formed by alveolar macrophages, which ingest and sequester the bacilli within granulomatous structures. The control and resolution of the infection involve the activation of macrophages, in which activated T lymphocytes play a crucial role [4]. The release of proinflammatory cytokines such as IL-1b, TNF, IL-12 or IL-18 from monocytes and monocyte-derived macrophages induces the production of T-cell-derived cytokines, most importantly IFN-g, which in turn will activate macrophages for the killing and elimination of the microorganisms [5,6]. Patients with defects in receptors for IL-12 and IFN have an increased susceptibility to mycobacterial infections [7][8][9], while the association between low CD4 counts and TB is well-known in HIV-infected patients [2].While most of the research has focused on the mechanisms resp...

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Innate Immunity toMycobacterium tuberculosis

Cited by 501 publications

References 254 publications

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

Transcriptional and inflammasome‐mediated pathways for the induction of IL‐1β production by Mycobacterium tuberculosis

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