Immune Defence: Microbial Interference

Abstract

To cause diseases, pathogens must first breach physical barriers and then successfully replicate and disseminate while avoiding destruction by immune system. The immune system control is achieved by two defence mechanisms: the innate immune defence, which consists in a non‐specific mechanism present in organisms across all kingdoms, and the adaptive immunity defence, acquired over time following infections or vaccination. Despite the sophisticated immune system, extracellular and intracellular pathogens have developed numerous, and often ingenious strategies, to evade, interfere or eradicate the effectiveness of host immune defences. Although the strategies used by viral and bacterial pathogens are numerous, there are several general mechanisms shared between these microbial pathogens. The success of each pathogen depends on the coordinated activities of its virulence factors to overcome host barriers to colonisation and its ability to mount an effective anti‐immune response within the infected host, which can ultimately result in acute disease or chronic infection.

Key Concepts

  • Immunoglobulin proteases cleave antibodies rendering them non‐functional and leading to deficiencies in the immune system.
  • Complement regulators prevent complement activation and cell destruction.
  • Interference with major histocompatibility complexes overcomes T‐cell recognition.
  • Microbial interference with cytokines modulates intracellular signalling critical to the regulation, proliferation and differentiation of lymphocytes, which drive inflammation.
  • Intracellular resistance allows microorganisms to circumvent humoral defence mechanisms and spread within the host.
  • Immunosuppression reduces T or B lymphocytes' defence.

Keywords: destruction of immune molecules; cytokine antagonists; phagocytic uptake; intracellular resistance; destruction of immune cells

Figure 1. Cleavage of human immunoglobulin A1 (IgA1) and A2 (IgA2) by IgA proteases. Red arrows show possible bacterial IgA1 protease target sites on the IgA1 heavy chain and green arrows shows IgA protease, which attack both IgA1 and IgA2.
Figure 2. Schematic outline of major histocompatibility complex (MHC) class I antigen processing. Points of interference for viral gene products are shown in the red boxes. ER, endoplasmic reticulum; TAP, transporter‐associated protein.
Figure 3. Schematic trafficking pathway of major histocompatibility complex (MHC) class II. Points of interference for viral gene products are shown in the red boxes. ADP, adenosine diphosphate; ATP, adenosine triphosphate; ER, endoplasmic reticulum; mRNA, messenger ribonucleic acid.
close

References

Ahn K , Gruhler A , Galoha B , et al. (1997) The ER‐luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Immunity 6: 613–621.

Bardoel BW , Vos R , Bouman T , et al. (2012) Evasion of Toll‐like receptor 2 activation by staphylococcal superantigen‐like protein 3. Journal of Molecular Medicine 90: 1109–1120.

Barrionuevo P , Cassataro J , Delpino MV , et al. (2008) Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through interleukin‐6 secretion via Toll‐like receptor 2. Infection and Immunity 76: 250–262.

Briken V , Porcelli SA , Besra GS and Kremer L (2004) Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Molecular Microbiology 53: 391–403.

Cirl C , Wieser A , Yadav M , et al. (2008) Subversion of Toll‐like receptor signaling by a unique family of bacterial Toll/interleukin‐1 receptor domain‐containing proteins. Nature Medicine 14: 399–406.

Coombes BK , Valdez Y and Finlay BB (2004) Evasive maneuvers by secreted bacterial proteins to avoid innate immune responses. Current Biology 14: R856–R867.

Crawford MA , Aylott CV , Bourdeau RW and Bokoch GM (2006) Bacillus anthracis toxins inhibit human neutrophils NADPH oxidase activity. Journal of Immunology 17: 7757–7765.

Flannagan RS , Cosío G and Grinstein S (2009) Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nature Reviews Microbiology 7: 355–366.

Gilbert MJ , Riddel SR , Plachter B and Greenberg PD (1996) Cytomegalovirus selectively blocks antigen processing and presentation of its immediate‐early gene product. Nature 383: 720–722.

Haraga A and Miller SI (2003) A Salmonella enterica serovar Typhimurium translocated leucine‐rich repeat effector protein inhibits NF‐κB‐dependent gene expression. Infection and Immunity 71: 4052–4058.

Henneke P and Golenbock DT (2004) Phagocytosis, innate immunity, and host‐pathogen specificity. Journal of Experimental Medicine 19: 1–4.

Horwitz MA and Maxfield FR (1984) Legionella pneumophila inhibits acidification of its phagosome in human monocytes. Journal of Cell Biology 99: 1936–1943.

Lacaille VG and Androlewicz MJ (1998) Herpes simplex virus inhibitor ICP47 destabilizes the transporter associated with antigen processing (TAP) heterodimer. Journal of Biological Chemistry 273: 17386–17390.

Langley R , Wines B , Willoughby N , et al. (2005) The staphylococcal superantigen‐like protein 7 binds IgA and complement C5 and inhibits IgA‐Fc alpha RI binding and serum killing of bacteria. Journal of Immunology 174: 2926–2933.

Lapaque N , Hutchinson JL , Jones DC , et al. (2009) Salmonella regulates polyubiquitination and surface expression of MHC class II antigens. Proceedings of the National Academy of Sciences of the United States of America 106: 14052–14057.

Lathem WW , Bergsbaken T and Welch RA (2004) Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by E. coli O157:H7. Journal of Experimental Medicine 199: 1077–1087.

Laurent‐Crawford AG , Krust B , Bivieri Y , et al. (1993) Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Research and Human Retroviruses 9: 761–773.

Lee LY et al. (2002) The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell mediated responses. Journal of Clinical Investigation 110: 1461–1471.

Levitskaya J , Shapiro A , Leonchiks A , Ciechanover A and Masucci MG (1997) Inhibition of ubiquitin/proteasome‐dependent protein degradation by the Gly Ala repeat domain of the Epstein–Barr virus nuclear antigen 1. Proceedings of the National Academy of Sciences of the United States of America 94: 12616–12621.

Liu M , Haenssler E , Uehara T , et al. (2012) The Legionella pneumophila EnhC protein interferes with immunostimulatory muramyl peptide production to evade innate immunity. Cell Host & Microbe 12: 166–176.

Mathews MB and Shenk T (1991) Adenovirus‐associated RNA and translation control. Journal of Virology 65: 5657–5662.

McGuirk P , McCann C and Mills KHG (2002) Pathogen‐specific T regulatory I cells induced in the respiratory tract by a bacteria molecule that stimulate interleukine 10 production by dendritic cells: a novel strategy for evasion of protective T helper I response by Bordetella pertussis. Journal of Experimental Medicine 195: 221–231.

Moore KW , Vieira P , Fiorentino DF , et al. (1990) Homology of cytokine synthesis inhibitory factor (IL‐10) to the Epstein–Barr virus gene BCRFI. Science 248: 1230–1234.

Navarro L , Alto NM and Dixon JE (2005) Functions of the Yersinia effector proteins in inhibiting host immune responses. Current Opinion in Microbiology 8: 21–27.

Newton HJ , Pearson JS , Badea L , et al. (2010) The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF‐kB p65. PLoS Pathogens 6: e1000898.

Olsen RL , Echtenkamp F , Cheranova D , et al. (2013) The enterohemorrhagic Escherichia coli effector protein NleF binds mammalian Tmp21. Veterinary Microbiology 164: 164–170.

Orth K , Xu Z , Mudgett MB , et al. (2000) Disruption of signaling by Yersinia effector YopJ, a ubiquitin‐like protein protease. Sciences 290: 1594–1597.

Paabo S , Nilsson T and Peterson PA (1986) Adenoviruses of genera B, C, D and E modulate cell‐surface expression of major histocompatibility complex class antigens. Proceedings of the National Academy of Sciences of the United States of America 83: 9665–9669.

Pausa M , Pellis V , Cinco M , et al. (2003) Serum‐resistant strains of Borrelia burgdorferi evade complement‐mediated killing by expressing a CD59‐like complement inhibitory molecule. Journal of Immunology 170: 3214–3222.

Piguet V , Schwartz O , Le Gall S and Trono D (1999) The downregulation of CD4 and MHC‐1 by primate lentiviruses: a paradigm for the modulation of cell surface receptors. Immunology Reviews 168: 51–63.

Plaut AG (1983) The IgA1 proteases of pathogenic bacteria. Annual Review of Microbiology 37: 603–622.

Portnoy DA (2005) Manipulation of innate immunity by bacterial pathogens. Current Opinion in Immunology 17: 25–28.

Ramu P , Tanskanen R , Holmberg M , et al. (2007) The surface protease PgtE of Salmonella enterica affects complement activity by proteolytically cleaving C3b, C4b and C5. FEBS Letters 581: 1716–1720.

Rooijakkers SH , van Wamel WJ , Ruyken M , van Kessel KP and van Strijp JA (2005a) Anti‐opsonic properties of staphylokinase. Microbes and Infection 7: 476–484.

Rooijakkers SHM , Ruyken M , Roos A , et al. (2005b) Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nature Immunology 6: 920–927.

Rosenberger CM and Finlay BB (2003) Phagocyte sabotage: disruption of macrophage signaling by bacterial pathogens. Nature Reviews Molecular Cell Biology 4: 385–396.

Sanada T , Kim M , Mimuro H , et al. (2012) The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. Nature 483: 623–626.

Schultz DR and Miller KD (1974) Elastase of Pseudomonas aeruginosa: inactivation of complement components and complement‐derived chemotactic and phagocytic factors. Infection and Immunity 10: 128–135.

Siliciano RF , Lawton T , Knall C , et al. (1988) Analysis of host–virus interactions in AIDS with anti‐gp T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell 54: 561–575.

Sing A , Roggenkamp A , Geiger AM and Heesemann J (2002) Yersinia enterocolitica evasion of the host innate immune response by V antigen‐induced IL‐10 production of macrophages is abrogate in IL‐10‐deficient mice. Journal of Immunology 168: 1315–1321.

Slevogt H , Zabel S , Opitz B , et al. (2008) CEACAM1 inhibits Toll‐like receptor 2‐triggered antibacterial responses of human pulmonary epithelial cells. Nature Immunology 9: 1270–1278.

Spriggs MK (1994) Poxvirus‐encoded soluble cytokine receptors. Virus Research 33: 1–10.

Tateda K , Ishii Y , Horikawa M , et al. (2003) The Pseudomonas aeruginosa autoinducer N‐3‐oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Infection and Immunity 71: 5785–5793.

Terao Y , Mori Y , Yamaguchi M , et al. (2008) Group A streptococcal cysteine protease degrades C3 (C3b) and contributes to evasion of innate immunity. Journal of Biological Chemistry 283: 6253–6260.

Thanabalasuriar A , Bergeron J , Gillingham A , et al. (2012) Sec24 interaction is essential for localization and virulence‐associated function of the bacterial effector protein NleA. Cellular Microbiology 14: 1206–1218.

Wheeler PR and Gregory D (1980) Superoxide dismutase, peroxidatic activity and catalase in Mycobacterium leprae purified from armadillo liver. Journal of General Microbiology 121: 457–464.

Wilson JE , Katkere B and Drake JR (2009) Francisella tularensis induces ubiquitin‐dependent major histocompatibility complex class II degradation in activated macrophages. Infection and Immunity 77: 4953–4965.

Zhong G , Liu L , Fan T , Fan P and Ji H (2000) Degradation of transcription factor RFX5 during the inhibition of both constitutive and interferon gamma‐inducible major histocompatibility complex class I expression in Chlamydia‐infected cells. Journal of Experimental Medicine 191: 1525–1534.

Further Reading

Alcami A (2003) Viral mimicry of cytokines, chemokines and their receptors. Nature Reviews Immunology 3: 36–50.

Brett Finlay B and McFadden G (2006) Anti‐immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124: 767–782.

Bloma AM , Hallströmb T and Riesbeckb K (2009) Complement evasion strategies of pathogens: acquisition of inhibitors and beyond. Molecular Immunology 46: 2808–2817.

Diacovich L and Gorvel JP (2010) Bacterial manipulation of innate immunity to promote infection. Nature Reviews Microbiology 8: 117–128.

Hansen TH and Bouvier M (2009) MHC class I antigen presentation: learning from viral evasion strategies. Nature Reviews Immunology 9: 503–513.

Johannessen M , Askarian F , Sangvik M and Sollid JE (2013) Bacterial interference with canonical NFkB signalling. Microbiology 159: 2001–2013.

Reddick LE and Alto NM (2014) Bacteria fighting back: how pathogens target and subvert the host innate immune system. Molecular Cell 54: 321–328.

Sen GC (2001) Viruses and interferons. Annual Review of Microbiology 55: 255–281.

Tortorella D , Gewurz BE , Furman MH , Schust DJ and Ploegh HL (2000) Viral subversion of the immune system. Annual Review of Immunology 18: 861–926.

Underhill DM and Ozinsky A (2002) Phagocytosis of microbes: complexity in action. Annual Review of Immunology 20: 825–852.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Merino, Susana, and Tomás, Juán M(Jul 2015) Immune Defence: Microbial Interference. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000487.pub4]