Abstract
Immunity to pneumonic plague is conferred to the host by the production of antibodies targeting LcrV, a component of the Yersinia pestis type III secretion system machinery. To achieve adequate protection, antibodies must be administered early during infection. In order to extend this period of time and better understand the mechanism of humoral immunity toward disease, we have been identifying host factors that contribute to the antibody-mediated clearance of bacteria. Anti-LcrV antibodies not only inhibit effector protein translocation into host cells, but also opsonize bacteria for uptake by phagocytes. Thus, we examined the protective efficacy of anti-LcrV antibodies in mice deficient for phagocyte recruitment and effector function. We have previously shown that mice deficient in neutrophil recruitment and activation cannot be protected by antibody treatment, indicating that this cell population is essential in clearing opsonized bacteria. Although anti-LcrV antibodies cannot protect these mice from challenge, an initial inhibition in bacterial replication and a delay in the time to death are observed. Thus, we hypothesized here that additional phagocyte populations and/or functions mediate early protection from disease in the presence of protective antibodies. We show that mice lacking monocyte chemoattractant protein-1 (MCP-1) are deficient in their ability to clear infection. Similar results are seen in mice lacking CCR2, the receptor for MCP-1. To examine phagocyte effector functions that may be contributing to direct killing of the organism, we tested mice lacking 5-lipoxygenase, an enzyme that mediates phagocytosis and inflammatory cell recruitment, and found it was dispensable for antibody protection. We also examined mice deficient in monocyte, macrophage, and granulocyte autophagy and found similar results. Taken together, the data suggest that humoral immunity to pneumonic plague requires activation of specific pathways of recruitment and activation of neutrophils and inflammatory monocytes.
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Acknowledgments
We would like to thank all of the members of the Anderson laboratory for technical assistance with BSL-3 experiments. We would also like to thank Dr. Herbert W. Virgin for graciously providing the ATG5 mice. NAE is supported by an NIH/NIGMS Cellular and Molecular Biology training grant (T32 GM008396). This work was funded in part by the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (U54 AI157160).
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Eisele, N.A., Brown, C.R., Anderson, D.M. (2012). Phagocytes and Humoral Immunity to Pneumonic Plague. In: de Almeida, A., Leal, N. (eds) Advances in Yersinia Research. Advances in Experimental Medicine and Biology, vol 954. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3561-7_21
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DOI: https://doi.org/10.1007/978-1-4614-3561-7_21
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