Molecular half-full mechanisms by phagocityc cells on invasive Aspergilosis
Main Article Content
Fungus from the Aspergillus genus mainly affects lung tissue, occurring when the integrity of the host immune system is compromised. The human body uses immunocompetence conditions from mechanical and enzymatic defenses and the action of the innate immune system cells and also uses adaptive responses to control infection.
Neutrophils, macrophages, and dendritic cells are critical as antifungal effector cells possess surface receptors that recognize fungal structures and trigger specific responses. TLRs and Dectin-1 the most studied for this interaction.
TLRs are responsible for the production and release of cytokines and Dectin-1 is essential in the phagocytosis of the particle recognition and production of ROS. The best-studied cytokines and its crucial role in the response to Aspergillus spp. are TNF-α, IFN-γ, and IL-12. In this work, we reviewed the main mechanisms related to molecular receptors on phagocytic cells involved in the recognition of Aspergillus spp. Understanding the immune response in situations of immunocompetence and its comparison in immunodeficient organisms could provide alternatives to control invasive aspergillosis.
- Aspergillus
- Immune system
- Toll-like receptors
- Dectin-1
- DC-SIGN
- MR and cytokines
Lumbreras C, Gavaldà J. Aspergilosis invasora: manifestaciones
clínicas y tratamiento. Rev Iberoam Micol. 2003; 20: 79-89. DOI: https://doi.org/10.1023/A:1024438130716
Patterson TF, Kirkpatrick WR, White M, Hiemenz JW,
Wingard JR, Dupont B, et al. Invasive aspergillosis. Disease
spectrum, treatment practices, and outcomes. I3 Aspergillus
Study Group. Medicine. 2000; 79: 250-60. DOI: https://doi.org/10.1097/00005792-200007000-00006
Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality
rate: systematic review of the literature. Clin Infect Dis. 2001;
: 358-66.
Silva RF. Infecções fúngicas em imunocomprometidos.
Capítulo 8. J Bras Pneumol. 2010; 36: 142-7. DOI: https://doi.org/10.1590/S1806-37132010000100019
Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol
Rev. 1999; 12: 310-50. DOI: https://doi.org/10.1128/CMR.12.2.310
Dagenais TRT, Keller NP. Pathogenesis of Aspergillus
fumigatus in invasive aspergillosis. Clin Microbiol Rev. 2009;
: 447-65.
Balloy V, Chignard M. The innate immune response to
Aspergillus fumigatus. Microbes Infect. 2009; 11: 919-27. DOI: https://doi.org/10.1016/j.micinf.2009.07.002
Zarember KA, Sugui JA, Chang YC, Kwon-Chung KJ,
Gallin JI. Human polymorphonuclear leukocytes inhibit
Aspergillus fumigatus conidial growth by lactoferrinmediated
iron depletion. J Immunol. 2007; 178: 6367-73. DOI: https://doi.org/10.4049/jimmunol.178.10.6367
Tkalcevic J, Novelli M, Phylactides M, Iredale JP, Segal AW,
Roes J. Impaired immunity and enhanced resistance to
endotoxin in the absence of neutrophil elastase and cathepsin
G. Immunity. 2000; 12: 201-10. DOI: https://doi.org/10.1016/S1074-7613(00)80173-9
Chen L, Shen Z, Wu J. Expression, purification and in vitro
antifungal activity of acidic mammalian chitinase against
Candida albicans, Aspergillus fumigatus and Trichophyton rubrum
strains. Clin Exp Dermatol. 2009; 34: 55-60.
Shoham S, Levitz SM. The immune response to fungal
infections. Br J Haematol. 2005; 129: 569-82. DOI: https://doi.org/10.1111/j.1365-2141.2005.05397.x
Philippe B, Ibrahim-Granet O, Prevost MC, Gougerot-
Pocidalo MA, Sánchez-Pérez M, Van der Meeren A, et al.
Killing of Aspergillus fumigatus by alveolar macrophages is
mediated by reactive oxidant intermediates. Infect Immun.
; 71: 3034-42.
Huang Q, Liu D, Majewski P, Schulte LC, Korn JM, Young
RA, et al. The plasticity of dendritic cell responses to
pathogens and their components. Science. 2001; 294: 870-5. DOI: https://doi.org/10.1126/science.294.5543.870
Romani L. Immunity to fungal infections. Nat Rev Immunol.
; 4: 11-24.
Banchereau J, Steinman RM. Dendritic cells and the control
of immunity. Nature. 1998; 392: 245-52. DOI: https://doi.org/10.1038/32588
Roilides E, Tsaparidou S, Kadiltsoglou I, Sein T, Walsh TJ.
Interleukin-12 enhances antifungal activity of human
mononuclear phagocytes against Aspergillus fumigatus:
implications for a gamma interferon-independent pathway.
Infect Immun. 1999; 67: 3047-50. DOI: https://doi.org/10.1128/IAI.67.6.3047-3050.1999
Romani L, Mencacci A, Tonnetti L, Spaccapelo R, Cenci E,
Puccetti P, et al. IL-12 is both required and prognostic in vivo
for T helper type 1 differentiation in murine candidiasis. J
Immunol. 1994; 153: 5167-75.
Cenci E, Mencacci A, Del Sero G, Bacci A, Montagnoli C,
d'Ostiani CF, et al. Interleukin-4 causes susceptibility to
invasive pulmonary aspergillosis through suppression of
protective type I responses. J Infect Dis. 1999; 180: 1957-68. DOI: https://doi.org/10.1086/315142
Del Sero G, Mencacci A, Cenci E, d'Ostiani CF, Montagnoli
C, Bacci A, et al. Antifungal type 1 responses are upregulated
in IL-10-deficient mice. Microbes Infect. 1999; 1: 1169-80. DOI: https://doi.org/10.1016/S1286-4579(99)00245-2
Roilides E, Dimitriadou A, Kadiltsoglou I. IL-10 exerts
suppressive and enhancing effects on antifungal activity of
mononuclear phagocytes against Aspergillus fumigatus. J
Immunol. 1997; 158: 322-9.
Romani L, Puccetti P, Bistoni F. Interleukin-12 in infectious
diseases. Clin Microbiol Rev. 1997; 10: 611-36. DOI: https://doi.org/10.1128/CMR.10.4.611
Steele C, Rapaka RR, Metz A, Pop SM, Williams DL,
Gordon S, et al. The beta-glucan receptor dectin-1 recognizes
specific morphologies of Aspergillus fumigatus. PLoS Pathog.
; 1: e42.
Gersuk GM, Underhill, David M, Zhu L, Marr KA. Dectin-
and TLRs permit macrophages to distinguish between
different Aspergillus fumigatus cellular states. J Immunol. 2006;
: 3717-24.
Mehrad B, Strieter RM, Standiford TJ. Role of TNF-alpha
in pulmonary host defense in murine invasive aspergillosis.
J Immunol. 1999; 162: 1633-40. DOI: https://doi.org/10.4049/jimmunol.162.3.1633
Bellanger AP, Millon L, Khoufache K, Rivollet D, Bieche I,
Laurendeau I, et al. Aspergillus fumigatus germ tube growth
and not conidia ingestion induces expression of inflammatory
mediator genes in the human lung epithelial cell line A549.
J Med Microbiol. 2009; 58: 174-9. DOI: https://doi.org/10.1016/j.srt.2009.03.016
Brieland JK, Jackson C, Menzel F, et al. Cytokine networking
in lungs of immunocompetent mice in response to inhaled
Aspergillus fumigatus. Infect Immun. 2001; 69: 1554-60. DOI: https://doi.org/10.1128/IAI.69.3.1554-1560.2001
Romani L. Immunity to fungal infections. Nat Rev Immunol.
; 11: 275-88.
Vautier S, Sousa Mda G, Brown GD. C-type lectins, fungi
and Th17 responses. Cytokine Growth Factor Rev. 2010; 21:
-12.
Huang W, Na L, Fidel PL, Schwarzenberger P. Requirement
of interleukin-17A for systemic anti-Candida albicans host
defense in mice. J Infect Dis. 2004; 190: 624-31. DOI: https://doi.org/10.1086/422329
Werner JL, Metz AE, Horn D, Schoeb TR, Hewitt MM,
Schwiebert LM, et al. Requisite role for the dectin-1 betaglucan
receptor in pulmonary defense against Aspergillus
fumigatus. J Immunol. 2009; 182: 4938-46. DOI: https://doi.org/10.4049/jimmunol.0804250
Zenaro E, Donini M, Dusi S. Induction of Th1/Th17
immune response by Mycobacterium tuberculosis: role of
dectin-1, Mannose Receptor, and DC-SIGN. J Leukoc Biol.
; 86: 1393-401.
van de Veerdonk FL, Marijnissen RJ, Kullberg BJ, Koenen
HJ, Cheng SC, Joosten I, et al. The macrophage mannose
receptor induces IL-17 in response to Candida albicans. Cell
Host Microbe. 2009; 5: 329-40.
Montagnoli C, Fallarino F, Gaziano R, Bozza S, Bellocchio
S, Zelante T, et al. Immunity and tolerance to Aspergillus
involve functionally distinct regulatory T cells and tryptophan
catabolism. J Immunol. 2006; 176: 1712-23. DOI: https://doi.org/10.4049/jimmunol.176.3.1712
Dubourdeau M, Athman R, Balloy V. Aspergillus fumigatus
induces innate immune responses in alveolar macrophages
through the MAPK pathway independently of TLR2 and
TLR4. J Immunol. 2006; 177: 3994-4001. DOI: https://doi.org/10.4049/jimmunol.177.6.3994
Feldmesser M. Role of neutrophils in invasive aspergillosis.
Infect Imm. 2006; 74: 6514-6. DOI: https://doi.org/10.1128/IAI.01551-06
Bozza S, Gaziano R, Spreca A, Bacci A, Montagnoli C, di
Francesco P, et al. Dendritic cells transport conidia and
hyphae of Aspergillus fumigatus from the airways to the
draining lymph nodes and initiate disparate Th responses to
the fungus. J Immunol. 2002; 168: 1362-71. DOI: https://doi.org/10.4049/jimmunol.168.3.1362
Bernard M, Latge JP. Aspergillus fumigatus cell wall:
composition and biosynthesis. Med Mycol. 2001; 39 Suppl 1: DOI: https://doi.org/10.1080/mmy.39.6.1.1
-17.
Fontaine T, Simenel C, Dubreucq G, Adam O, Delepierre
M, Lemoine J, et al. Molecular organization of the alkaliinsoluble
fraction of Aspergillus fumigatus cell wall. J Bioll
Chem. 2000; 275: 27594-607. DOI: https://doi.org/10.1074/jbc.M909975199
Lavigne LM, Albina JE, Reichner JS. Beta-glucan is a fungal
determinant for adhesion-dependent human neutrophil
functions. J Immunol. 2006; 177: 8667-75. DOI: https://doi.org/10.4049/jimmunol.177.12.8667
Meier A, Kirschning CJ, Nikolaus T, Wagner H, Heesemann
J, Ebel F. Toll-like receptor (TLR) 2 and TLR4 are essential
for Aspergillus-induced activation of murine macrophages.
Cell Microbiol. 2003; 5: 561-70. DOI: https://doi.org/10.1046/j.1462-5822.2003.00301.x
Hohl TM, Van Epps HL, Rivera A, Morgan LA, Chen PL,
Feldmesser M, et al. Aspergillus fumigatus triggers inflammatory
responses by stage-specific beta-glucan display. PLoS Pathog.
; 1: e30.
Brown GD, Herre J, Williams DL, Willment JA, Marshall
AS, Gordon S. Dectin-1 mediates the biological effects of
beta-glucans. J Exp Med. 2003; 197: 1119-24. DOI: https://doi.org/10.1084/jem.20021890
Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill
DM. Collaborative induction of inflammatory responses by
dectin-1 and Toll-like receptor 2. J Exp Med. 2003; 197:
-17.
Mambula SS, Sau K, Henneke P, Golenbock DT, Levitz
SM. Toll-like receptor (TLR) signaling in response to
Aspergillus fumigatus. J Biol Chem. 2002; 277: 39320-6. DOI: https://doi.org/10.1074/jbc.M201683200
Netea MG, Warris A, Van der Meer JW, Fenton MJ, Verver-
Janssen TJ, Jacobs LE, et al. Aspergillus fumigatus evades
immune recognition during germination through loss of
toll-like receptor-4-mediated signal transduction. J Infect
Dis. 2003; 188: 320-6.
Luther K, Torosantucci A, Brakhage AA, Heesemann J,
Ebel F. Phagocytosis of Aspergillus fumigatus conidia by
murine macrophages involves recognition by the Dectin-1
beta-glucan receptor and Toll-like receptor 2. Cell Microbiol.
; 9: 368-81.
Taylor PR, Brown GD, Reid DM, Willment JA, Martínez-
Pomares L, et al. The beta-glucan receptor, dectin-1, is
predominantly expressed on the surface of cells of the
monocyte/macrophage and neutrophil lineages. J Immunol.
; 169: 3876-82.
Willment JA, Marshall AS, Reid DM, Williams DL, Wong
SY, Gordon S, et al. The human beta-glucan receptor is
widely expressed and functionally equivalent to murine
Dectin-1 on primary cells. Eur J Immunol. 2005; 35: 1539-47. DOI: https://doi.org/10.1002/eji.200425725
Reid DM, Gow NA, Brown GD. Pattern recognition:
recent insights from Dectin-1. Curr Opin Immunol. 2009; 21:
-7.
Brown GD, Taylor PR, Reid DM, Willment JA, Williams
DL, Martínez-Pomares L, et al. Dectin-1 is a major betaglucan
receptor on macrophages. J Exp Med. 2002; 196: 407-12. DOI: https://doi.org/10.1084/jem.20020470
Brown GD, Gordon S. Immune recognition. A new receptor
for beta-glucans. Nature. 2001; 413: 36-7. DOI: https://doi.org/10.1038/35092620
Dennehy KM, Ferwerda G, Faro-Trindade I, Pyz E, Willment
JA, Taylor PR, et al. Syk kinase is required for collaborative
cytokine production induced through Dectin-1 and Tolllike
receptors. Eur J Immunol. 2008; 38: 500-6.
Serrano-Gómez D, Domínguez-Soto A, Ancochea J,
Jiménez-Heffernan JA, Leal JA, Corbi AL. Dendritic cellspecific
intercellular adhesion molecule 3-grabbing nonintegrin
mediates binding and internalization of Aspergillus
fumigatus conidia by dendritic cells and macrophages. J
Immunol. 2004; 173: 5635-43.
Gazi U, Rosas M, Singh S, Heinsbroek S, Haq I, Johnson S,
et al. Fungal recognition enhances mannose receptor shedding
through dectin-1 engagement. J Biol Chem. 2011; 286: 7822- DOI: https://doi.org/10.1074/jbc.M110.185025
Ibrahim-Granet O, Philippe B, Boleti H, Boisvieux-Ulrich
E, Grenet D, Stern M, et al. Phagocytosis and intracellular
fate of Aspergillus fumigatus conidia in alveolar macrophages.
Infect Immun. 2003; 71: 891-903. DOI: https://doi.org/10.1128/IAI.71.2.891-903.2003
Cathcart MK. Regulation of superoxide anion production
by NADPH oxidase in monocytes/macrophages: contributions
to atherosclerosis. Arterioscler Thromb Vasc Biol.
; 24: 23-8.
Underhill DM, Rossnagle E, Lowell CA, Simmons RM.
Dectin-1 activates Syk tyrosine kinase in a dynamic subset
of macrophages for reactive oxygen production. Blood. 2005;
: 2543-50.
Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M,
Findon H, et al. Dectin-1 is required for beta-glucan
recognition and control of fungal infection. Nat Immunol.
; 8: 31-8.
Aratani Y, Kura F, Watanabe H, Akagawa H, Takano Y,
Suzuki K, et al. in vivo role of myeloperoxidase for the host
defense. Jpn J Infect Dis. 2004; 57: S15.
Downloads
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use