Pneumocystis: Immune recognition and evasion

Pop, Shannon M.; Kolls, Jay K.; Steele, Chad

doi:10.1016/j.biocel.2005.08.010

Cited by 13 publications

(5 citation statements)

References 33 publications

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“…Despite its reported ability to recognize fungi like Candida albicans, Cryptococcus neoformans, and Pneumocystis, little is known about the role of MR as a PRR for A. fumigatus (3,6,26). This is intriguing given that terminal mannose, fucose, and N-acetylglucosamine are established ligands for MR (35) and such mannose-based moieties are a major component of the Aspergillus cell wall (15).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses byAspergillus fumigatus

Chai

Kullberg²,

Vonk

et al. 2009

Infect Immun

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Toll-like receptor (TLR)-based signaling pathways in the host may be modulated by pathogens during the course of infection. We describe a novel immunomodulatory mechanism in which Aspergillus fumigatus conidia induce attenuation of TLR2-and TLR4-mediated interleukin (IL)-6 and IL-1␤ proinflammatory responses in human mononuclear cells with suppression of IL-1␤ mRNA transcription. Background TLR2 and TLR4 mRNA transcription was not influenced. A. fumigatus conidia induced TLR2 internalization and uptake into the phagosome with a resultant decrease in surface receptor expression. A. fumigatus hyphae, on the other hand, selectively downregulated the TLR4-mediated response. These novel immunosuppressive effects may facilitate the invasiveness of A. fumigatus.Opportunistic fungal infections remain a significant cause of mortality and morbidity in immunocompromised patients. Aspergillus fumigatus is one of the most common infective molds worldwide (7). Acquisition of invasive aspergillosis results from inhalation of airborne conidia, which, in the absence of competent immune containment, is followed by germination, development of hyphae, and invasive disease.Mononuclear phagocytes constitute an important component of host defense against A. fumigatus and also are the precursors of tissue macrophages involved in immune surveillance against invasive pulmonary aspergillosis (29, 31). Their ability to detect specific pathogen-associated molecular patterns of Aspergillus conidia involves expression of pathogen recognition receptors (PRRs), and the main families of these receptors are the Toll-like receptors (TLRs) and the lectin receptors. TLR2 and TLR4 have been reported to mediate recognition of various cell wall components of Aspergillus (2,18,19,40), and dectin-1, a C-type lectin receptor, is the major PRR involved in the recognition of ␤-glucans (21, 29, 32). Although infection experiments with TLR-deficient mice have provided evidence for involvement of TLR2 and TLR4 in the host defense against A. fumigatus (1, 2), the relative importance of both these receptors and other TLRs remains to be determined. In addition, the inflammatory response triggered through TLR2 and TLR4 strongly depends on the Aspergillus morphotype. For example, while conidium recognition was mediated by both TLR2 and TLR4, TLR4-mediated signaling was lost in recognition of hyphae (24). This inability to recognize and fight the most dangerous morphotype could represent an immune evasion mechanism (23). On the other hand, very little is known about whether fungal pathogens can also modulate a TLR-mediated host defense by decreasing the capacity of host cells to respond to TLR2 and TLR4 ligands.The aim of the present study was to study the capacity of A. fumigatus to modulate the host immune response triggered by TLRs. The effects of Aspergillus modulation of TLR2 and TLR4 activation were specifically examined, given that these receptors mediate the major pathways implicated in antifungal host defense. MATERIALS AND METHODSReagents. The TLR2 ligand ...

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Section: Discussionmentioning

confidence: 99%

Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses byAspergillus fumigatus

Chai

Kullberg²,

Vonk

et al. 2009

Infect Immun

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“…In addition to the various strategies such as morphogenic switching that are involved in masking cell wall PAMPS and preventing recognition by specific PRR, fungi have developed several other mechanisms to avoid, modulate and/ or suppress the induction of protective inflammatory responses. P. carinii , for example, may avoid MR-mediated recognition by secreting a MR-binding glycoprotein and by enhancing shedding of the MR from phagocytes (129). Fungi, such as C. albicans, can modulate inflammatory responses by targeting receptors, including DC-SIGN, FcγR, CR3 and TLR2, to induce the production of immunosuppressive cytokines, such as IL-10.…”

Section: Fungi Prrs and The Induction Of Soluble Mediatorsmentioning

confidence: 99%

Innate Antifungal Immunity: The Key Role of Phagocytes

Brown

2011

Annu. Rev. Immunol.

352

383

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Fungal diseases have emerged as significant causes of morbidity and mortality, particularly in immune compromised individuals, prompting greater interest in understanding the mechanisms of host resistance to these pathogens. Consequently, the last few decades have seen a tremendous increase in our knowledge of the innate and adaptive components underlying the protective (and non-protective) mechanisms of anti-fungal immunity. What has emerged from these studies is that phagocytic cells are essential for protection, and that defects in these cells compromises the hosts ability to resist fungal infection. This review covers the functions of phagocytes in innate antifungal immunity, along with selected examples of the strategies that are used by fungal pathogens to subvert these defences.

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“…The diversity within the genus became clear when DNA sequence analysis established that Pneumocystis is species specific, with each host species harboring a distinct genetic variation of the organism [1,2]. The Pneumocystis organism whose primary host is man was renamed Pneumocystis jirovecii, in honor of Otto Jirovec, who is credited with describing the microbe in humans [3], with the rat-specific fungus termed Pneumocystis carinii , and the mouse Pneumocystis murina [4].…”

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confidence: 99%

Current Understanding of Pneumocystis Immunology

Kelly

Shellito

2009

Future Microbiol.

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Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP.

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Pneumocystis: Immune recognition and evasion

Cited by 13 publications

References 33 publications

Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses byAspergillus fumigatus

Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses byAspergillus fumigatus

Innate Antifungal Immunity: The Key Role of Phagocytes

Current Understanding of Pneumocystis Immunology

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