Effect of Cytokine Interplay on Macrophage Polarization during Chronic Pulmonary Infection with Cryptococcus neoformans

Arora, Sarika; Olszewski, Michal A.; Tsang, Tiffany; McDonald, Roderick A.; Toews, Galen B.; Huffnagle, Gary B.

doi:10.1128/iai.01270-10

Cited by 125 publications

(160 citation statements)

References 42 publications

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“…To further test this, BALB/c mice were infected with H99 or the C. neoformans clinical isolate 52D. Experimental pulmonary infection with 52D is generally controlled in BALB/c mice (33,43). We observed no significant difference in pDC recruitment to the lungs between mice infected with 52D and mice infected with H99 (data not shown).…”

Section: Pdcs Inhibit Cryptococcal Growth In Vitromentioning

confidence: 76%

“…To elucidate the mechanism used by pDCs to inhibit the growth of C. neoformans, known mediators of anticryptococcal activity were tested. Nitric oxide (NO) has been shown to be important in the control of cryptococcal infection in phagocytic cells (31)(32)(33)(34). The enzyme responsible for the production of NO in phagocytic cells is inducible nitric oxide synthase (iNOS).…”

Section: Pdcs Inhibit Cryptococcal Growth In Vitromentioning

confidence: 99%

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Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformans In Vitro Requires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

et al. 2016

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dConventional dendritic cells (cDCs) are critical for protection against pulmonary infection with the opportunistic fungal pathogen Cryptococcus neoformans; however, the role of plasmacytoid dendritic cells (pDCs) is unknown. We show for the first time that murine pDCs have direct activity against C. neoformans via reactive oxygen species (ROS), a mechanism different from that employed to control Aspergillus fumigatus infections. The anticryptococcal activity of murine pDCs is independent of opsonization but appears to require the C-type lectin receptor Dectin-3, a receptor not previously evaluated during cryptococcal infections. Human pDCs can also inhibit cryptococcal growth by a mechanism similar to that of murine pDCs. Experimental pulmonary infection of mice with a C. neoformans strain that induces protective immunity demonstrated that recruitment of pDCs to the lungs is CXCR3 dependent. Taken together, our results show that pDCs inhibit C. neoformans growth in vitro via the production of ROS and that Dectin-3 is required for optimal growth-inhibitory activity.

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Section: Pdcs Inhibit Cryptococcal Growth In Vitromentioning

confidence: 76%

Section: Pdcs Inhibit Cryptococcal Growth In Vitromentioning

confidence: 99%

Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformans In Vitro Requires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

et al. 2016

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“…Our prior studies showed that pulmonary clearance in infected lungs correlates well with the type of the adaptive immune response (11,13,(18)(19)(20). Thus, we analyzed cytokine profiles in lung homogenates at weeks 1, 2, and 3 postinfection.…”

Section: Resultsmentioning

confidence: 99%

“…The role of Th17 responses is less clear, but studies suggest that interleukin 17 (IL-17) could contribute to protection against C. neoformans (16)(17)(18)(19). Indeed, most recent studies demonstrate that the overall balance between multiple cytokine responses in C. neoformans-infected lungs translates into outcomes that range from successful fungal clearance to the development of a chronic "steady-state" infection or a progressive, lethal infection (11,13,(20)(21)(22)(23). In summary, these studies document that the innate mechanisms of the immune response on their own are insufficient to contain the microbe following infection and that adaptive Th immunity needs to be properly polarized to provide effective control of the pathogen.…”

mentioning

confidence: 99%

Cryptococcus neoformans Growth and Protection from Innate Immunity Are Dependent on Expression of a Virulence-Associated DEAD-Box Protein, Vad1

2013

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The fungus Cryptococcus neoformans has emerged as a major cause of meningoencephalitis worldwide. Host response to the fungus involves both innate and adaptive immunity, but fungal genes that modulate these processes are poorly understood. Previous studies demonstrated attenuated virulence of a mutant of a virulence-associated DEAD-box protein (VAD1) in mice, despite normal growth at host temperatures, suggesting modulation of the immune response. In the present study, the ⌬vad1 mutant demonstrated progressive clearance from lung and was unable to induce pathological lesions or to cause extrapulmonary disease, despite retaining its ability to grow in mouse serum and a J774.

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“…Specifically, a Th1/Th17 cytokine profile has been shown to activate macrophage anticryptococcal activities, while a Th2 profile is associated with cryptococcal dissemination and host damage (17,37,68,69). Comparison of lung cytokine and chemokine profiles showed that the B6.CBA-Cnes2 strain had higher expression of proinflammatory mediators (IL-6, IL-1␤, and TNF-␣) than C57BL/6 mice at day 7 and day 14 postinfection.…”

Section: Fig 9 Characterization Of Serum Antibody Responses Followingmentioning

confidence: 99%

TheCnes2Locus on Mouse Chromosome 17 Regulates Host Defense against Cryptococcal Infection through Pleiotropic Effects on Host Immunity

et al. 2015

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The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. neoformans susceptibility (Cnes1, Cnes2, and Cnes3). To validate and characterize the role of Cnes2 during the host response, we constructed a congenic strain on the C57BL/6 background (B6.CBA-Cnes2). Phenotypic analysis of B6.CBA-Cnes2 mice 35 days after C. neoformans infection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-␥) and interleukin-12 (IL-12), lower expression of IL-4, IL-5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b؉ dendritic cells, and CD4 ؉ cells in B6.CBA-Cnes2 than in C57BL/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-Cnes2 mice. Taken together, these findings demonstrate that the Cnes2 interval is a potent regulator of host defense, immune responsiveness, and differential Th1/Th2 polarization following C. neoformans infection.

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Effect of Cytokine Interplay on Macrophage Polarization during Chronic Pulmonary Infection with Cryptococcus neoformans

Cited by 125 publications

References 42 publications

Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformans In Vitro Requires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformans In Vitro Requires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

Cryptococcus neoformans Growth and Protection from Innate Immunity Are Dependent on Expression of a Virulence-Associated DEAD-Box Protein, Vad1

TheCnes2Locus on Mouse Chromosome 17 Regulates Host Defense against Cryptococcal Infection through Pleiotropic Effects on Host Immunity

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