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NADPH oxidase, Nramp1 and nitric oxide synthase 2 in the host antimicrobial response

journal contribution
posted on 2023-05-23, 00:00 authored by Gunasegaran KarupiahGunasegaran Karupiah, Hunt, NH, King, NJ, Chaudhri, G
Using highly conserved, complex enzyme systems, leukocytes utilize the toxic nature of free radical intermediates, derived from oxygen and nitrogen, to control microbial pathogens as part of the innate immune response. Upon activation, NADPH oxidase generates superoxide anion radicals, which in turn give rise to further reactive oxygen intermediates. Similarly, activated nitric oxide synthase 2 catalyses the production of nitric oxide radicals, which leads to the formation of reactive nitrogen intermediates. Nitrogen- and oxygen-centered reactive intermediates can interact to form further reactive species. In addition, presence of the cationic transporter, Nrampl, may exacerbate the effects of these toxic compounds on invading microbes. While each of these antimicrobial systems can operate independently, the combination of their activities is synergistic in the successful containment of almost all invading pathogens. These systems are activated and modulated by microbial products and a series of temporally expressed cytokines. They also feed directly into the initiation of the adaptive immune response, which culminates in lasting specific immunity. The effector molecules, generated in the early innate immune response, are not specific to the invading pathogen and may also cause damage to the host. It is the critical balance of these processes in the initial stages of infection that determines the outcome of infectious disease.

History

Publication title

Reviews In Immunogenetics

Pagination

387-415

ISSN

1398-1714

Department/School

Tasmanian School of Medicine

Publisher

Munksgaard

Place of publication

Denmark

Repository Status

  • Restricted

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions

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