Cytokine enhancement of complement‐dependent phagocytosis by macrophages: synergy of tumor necrosis factor‐α and granulocyte‐macrophage colony‐stimulating factor for phagocytosis of <i>Cryptococcus neoformans</i>

Collins, Helen; Bancroft, Gregory J.

doi:10.1002/eji.1830220617

Cited by 168 publications

(103 citation statements)

References 41 publications

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“…neoformans activates the alternative complement pathway (14,16), which results in the deposition of C3 fragments on the surface of the microorganism, mostly in the form of iC3b (15,16). iC3b acts as the major opsonic component for phagocytosis of this microorganism by phagocytic leukocytes through binding to CR3 (Mac-1) (2,17,18). In the present study, the mAb that recognizes the α chain (CD11b) of CR3 significantly suppressed the dissemination of C. neoformans from the lung to the brain.…”

Section: Resultssupporting

confidence: 48%

Anti‐CD11b Monoclonal Antibody Suppresses Brain Dissemination of Cryptococcus neoformans in Mice

Kawakami

Koguchi

Qureshi

et al. 2002

Microbiology and Immunology

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To elucidate the role of the β2 integrin family of adhesion molecules in the disseminated infection of Cryptococcus neoformans from the lung to the central nervous system, we examined the effects of monoclonal antibodies (mAbs) against CD11a, CD11b, CD11c and CD18 on the number of live microorganisms in both the lung and brain of mice three weeks after intratracheal infection. Administration of anti‐CD11b mAb partially, but reproducibly, reduced the fungal loads in the brain in three independent experiments, while the lung loads were not affected. In addition, the same treatment significantly decreased the number of live microorganisms in the blood. In sharp contrast, the brain loads one week after intravenous injection with C. neoformans were not affected by treatment with anti‐CD11b mAb. Finally, administration of mAb against other adhesion molecules (CD11a, CD11c or CD18) failed to affect the fungal loads in the brain as well as in the lung three weeks after intratracheal instillation, except for anti‐CD18 mAb which rather increased the brain loads. Our results suggested that CD11b might be involved at least in part in the process of fungal dissemination from lung to brain, although the significance of other β2 integrin family adhesion molecules remains to be substantiated.

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Section: Resultssupporting

confidence: 48%

Anti‐CD11b Monoclonal Antibody Suppresses Brain Dissemination of Cryptococcus neoformans in Mice

Kawakami

Koguchi

Qureshi

et al. 2002

Microbiology and Immunology

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“…The importance of the T1 cytokine IFN-␥ is well established. IFN-␥ mediates M activation and C. neoformans killing in vitro, and animals depleted of IFN-␥ by Ab treatment are unable to defend against C. neoformans in vivo (18,19,(32)(33)(34). It is likely that the poor intracellular killing evident in M from uPA Ϫ/Ϫ mice in vivo is largely due to diminished IFN-␥-stimulation.…”

Section: Discussionmentioning

confidence: 99%

Urokinase-Type Plasminogen Activator Is Required for the Generation of a Type 1 Immune Response to PulmonaryCryptococcus neoformansInfection

Gyetko¹,

Sud²,

Chen³

et al. 2002

The Journal of Immunology

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Urokinase-type plasminogen activator (uPA)−/− mice cannot mount protective host defenses during infection with the opportunistic yeast Cryptococcus neoformans (52D). Because effective host defense against C. neoformans requires specific immune responses and the generation of type 1 (T1) cytokines, we determined how the absence of uPA impacts these processes. Wild-type (WT) and uPA−/− mice were inoculated with C. neoformans. Macrophage antifungal activity was assessed histologically, T lymphocyte responses in vivo and proliferation in vitro were quantified, and cytokine concentrations were determined by ELISA. uPA−/− macrophages have impaired antimicrobial activity. Regional lymph nodes of infected uPA−/− mice contained fewer cells than WT, suggesting impaired T cell proliferation in response to the pathogen in vivo. In vitro, uPA−/− T lymphocytes had impaired proliferative responses to C. neoformans rechallenge compared with WT. Infected WT mice generated T1 cytokines in the lung, characterized by high levels of IFN-γ and IL-12. uPA−/− mice had decreased levels of IFN-γ and IL-12, and increased IL-5, a type 2 cytokine. In the absence of uPA, the cytokine profile of regional lymph nodes shifted from a T1 pattern characterized by IFN-γ and IL-2 to a weak, nonpolarized response. We conclude that in the absence of uPA, lymphocyte proliferative responses are diminished, and mice fail to generate protective T1 cytokines, resulting in impaired antimicrobial activity. This study provides novel evidence that uPA is a critical modulator of immune responses and of immune cell effector functions in vivo.

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“…Collins & Bancroft [37] reported the involvement of TNF-in host resistance against C. neoformans by demonstrating increased mortality of infected mice by treatment with TNF--neutralizing MoAb. These results are inconsistent with the present findings, and may be due to two different strains of the fungus.…”

Section: Discussionmentioning

confidence: 99%

Contribution of tumour necrosis factor-alpha (TNF-α) in host defence mechanism against Cryptococcus neoformans

Kawakami

Xie

Tohyama

et al. 1996

Clinical and Experimental Immunology

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SUMMARYWe investigated the role of TNF-in the host defence mechanism against infection with a virulent strain of Cryptococcus neoformans. Administration of exogenous recombinant human TNF-significantly prolonged the survival time of mice infected by intratracheal instillation of the organism. Surprisingly, neutralizing MoAb to murine TNF-did not shorten their survival time, a finding inconsistent with previous results. To investigate the cause of this inconsistency, we examined the production of TNFin the lungs of infected mice. During the course of cryptococcosis, there was little or no generation of TNF-mRNA in the lung. This might be partly due to a direct inhibitory action of the fungal microorganism on TNF-production by macrophages. In vitro production of TNF-by murine interferon-gamma (IFN-)-and lipopolysaccharide (LPS)-stimulated macrophages was strongly inhibited by co-culturing with the whole yeast cells. In contrast, administration of recombinant murine IL-12 markedly induced TNF-production and the neutralizing anti-TNF-MoAb strongly blocked IL-12-induced protection of mice against cryptococcal infection. These results indicate that endogenously synthesized TNF-has the potential to contribute to the elimination of C. neoformans and partly mediates the protective effect of IL-12.

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Cytokine enhancement of complement‐dependent phagocytosis by macrophages: synergy of tumor necrosis factor‐α and granulocyte‐macrophage colony‐stimulating factor for phagocytosis of Cryptococcus neoformans

Cited by 168 publications

References 41 publications

Anti‐CD11b Monoclonal Antibody Suppresses Brain Dissemination of Cryptococcus neoformans in Mice

Anti‐CD11b Monoclonal Antibody Suppresses Brain Dissemination of Cryptococcus neoformans in Mice

Urokinase-Type Plasminogen Activator Is Required for the Generation of a Type 1 Immune Response to PulmonaryCryptococcus neoformansInfection

Contribution of tumour necrosis factor-alpha (TNF-α) in host defence mechanism against Cryptococcus neoformans

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