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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v26.i5.30
pages 407-442

Host Immune Responses to the Intracellular Bacteria Brucella: Does the Bacteria Instruct the Host to Facilitate Chronic Infection?

Cynthia L. Baldwin
Department of Veterinary and Animal Sciences, Paige Laboratory, University of Massachusetts, Amherst, MA 01003
Radhika Goenka
Department of Veterinary and Animal Sciences, Paige Laboratory, University of Massachusetts, Amherst, MA 01003

ABSTRACT

Brucella spp. are intracellular gram-negative bacteria that include a number of virulent species that cause chronic infections in a variety of mammalian hosts. Human infections are proportional to the level of disease in domestic animals because humans are infected zoonotically after contact with infected animals or their products. The chronicity of infection results from the ability of some brucellae to survive reactive oxygen intermediate and nitric oxide killing in host phagocytes, following which they activate bacterial genes in response to the acidic phagosome environment, prevent phagolysosomal fusion by remodeling the intracellular compartment, and subsequently replicate intracellularly. The crucial component of immunity that results in survival of the host and thus maintenance of this chronic infective state is interferon-γ (IFN-γ). Production of IFN-γ results from the ability of brucella components, including lipid A, to interact with Toll-like receptors for the production of IL-12 and TNF-α, although the regulatory cytokine IL-10 is also produced and decreases control of the infection. Although CD4 and CD8 T cells are clearly involved in the production of IFN-γ, and CD8 T cells may be cytotoxic, a role for NK cells and cytotoxicity in protective immunity to brucellosis has not been substantiated experimentally. Moreover, antibodies have been shown to have a limited role in passive transfer studies.


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