**8. Biotechnological applications of molecules involved in the recognition of pathogens**

Our growing understanding of host-pathogen interactions and mechanisms of protective immunity have allowed for an increasingly rational approach to the design of immune based therapeutics. One posible biomedical application of the discovery of efficient patho‐ gen receptors could be the generation of "immunoadhesins" (Perez de la Lastra et al., 2009). Because of the versatility of immunoadhesins, immunoadhesin-based therapies could, in theory, be developed against any existing pathogen. Some advantages of immunoadhesinbased therapies include versatility, low toxicity, pathogen specificity, enhancement of im‐ mune function, and favorable pharmacokinetics; the disadvantages include high cost, limited usefulness against mixed infections and the need for early and precise microbiologic diagnosis.

The patent by Visintin *et al*. (cited in Perez de la Lastra et al., 2009) discloses anti-pathogen immunoadhesins (APIs), a subset of which is "tollbodies", which have a pathogen recogni‐ tion module derived from the binding domain of a toll-like receptor (TLR). A schematic il‐ lustration of an exemplary API is shown in Fig. 11.

**Figure 11.** Schematic structure of an anti-pathogen immunoadhesin (API). Gray undashed area, pathogen recognition module; dashed, Fc portion. Disulfide bridges are represented by dashed line, which include intrachain bridges (that stabilize the Ig domains) and the interchain bridges (that covalently link two immunoadhesin molecules).

APIs can be used as therapeutics, e.g., for treating pathogen-associated disorders, e.g., infec‐ tions and inflammatory conditions (e.g. inflammatory conditions associated with a patho‐

gen- associated infection) and other disorders in which it is desirable to inhibit signaling pathways associated with the pathogen recognition protein from which the extracellular do‐ main of the API is derived. These APIs are particularly useful therapeutics because patho‐ gens generally cannot mutate the PAMPs (e.g., LPS) that are recognized by the pathogen recognition proteins. Thus, APIs can be used as antipathogenic agents to whom the targeted pathogen cannot develop resistance. The APIs can thus be used both *in vivo* and *in vitro/ex vivo*, e.g. to remove pathogens from blood or a water supply, or other liquids to be con‐ sumed, e.g., beverages, or even in the air, e.g. to combat a weapon of biological warfare. It is envisaged that these immunotechnological advances will increase the available antiinfective armamentarium and that immunoadhesin-therapy is poised to play an important part in modern anti-infective drugs.

[5] Bourne, H.R., D.A. Sanders and F. McCornick, The GTPase superfamily: conserved

Identification of Key Molecules Involved in the Protection of Vultures Against Pathogens and Toxins

http://dx.doi.org/10.5772/54191

263

[6] Brown, K., et al., The signal response of IkappaB alpha is regulated by transferable

[7] Desterro, J.M., M.S. Rodriguez, and R.T. Hay, SUMO-1 modification of IkappaBalpha

[8] Eidels, L., R.L. Proia and D.A. Hart, Membrane receptors for bacterial toxins. Micro‐

[9] Friedman, R. and A.L. Hughes, Molecular evolution of the NF-kappaB signaling sys‐

[10] Ghosh, S., M.J. May, and E.B. Kopp, NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol, 1998. 16: p. 225-60.

[11] Gilmore, T.D., Introduction to NF-kappaB: players, pathways, perspectives. Onco‐

[12] Hayden, M.S., A.P. West, and S. Ghosh, NF-kappaB and the immune response. On‐

[13] Hopkins, P.A. and S. Sriskandan, Mammalian Toll-like receptors: to immunity and

[14] Houston, D.C. and J.E. Cooper, The digestive tract of the whiteback griffon vulture and its role in disease transmission among wild ungulates. J Wildl Dis, 1975. 11(3): p.

[15] Huguet, C., P. Crepieux, and V. Laudet, Rel/NF-kappa B transcription factors and I kappa B inhibitors: evolution from a unique common ancestor. Oncogene, 1997.

[16] Jaffray, E., K.M. Wood, and R.T. Hay, Domain organization of I kappa B alpha and sites of interaction with NF-kappa B p65. Mol Cell Biol, 1995. 15(4): p. 2166-72.

[17] Johnson, G.B., et al., Evolutionary clues to the functions of the Toll-like family as sur‐

[18] Karin, M. and Y. Ben-Neriah, Phosphorylation meets ubiquitination: the control of

[19] Krishnan, V.A., et al., Structure and regulation of the gene encoding avian inhibitor

[20] Luque, I. and C. Gelinas, Distinct domains of IkappaBalpha regulate c-Rel in the cy‐

structure and molecular mechanism. Nature, 1991. 349: p. 117-126.

N- and C-terminal domains. Mol Cell Biol, 1997. 17(6): p. 3021-7.

inhibits NF-kappaB activation. Mol Cell, 1998. 2(2): p. 233-9.

tem. Immunogenetics, 2002. 53(10-11): p. 964-74.

beyond. Clin Exp Immunol, 2005. 140(3): p. 395-407.

veillance receptors. Trends Immunol, 2003. 24(1): p. 19-24.

NF-[kappa]B activity. Annu Rev Immunol, 2000. 18: p. 621-63.

of nuclear factor kappa B-alpha. Gene, 1995. 166(2): p. 261-6.

toplasm and in the nucleus. Mol Cell Biol, 1998. 18(3): p. 1213-24.

biol Rev, 1983. 47: p. 596-620.

gene, 2006. 25(51): p. 6680-4.

306-13.

15(24): p. 2965-74.

cogene, 2006. 25(51): p. 6758-80.
