Dermal Neutrophil, Macrophage and Dendritic Cell Responses to Yersinia pestis Transmitted by Fleas

Abstract

Yersinia pestis, the causative agent of plague, is typically transmitted by the bite of an infected flea. Many aspects of mammalian innate immune response early after Y. pestis infection remain poorly understood. A previous study by our lab showed that neutrophils are the most prominent cell type recruited to the injection site after intradermal needle inoculation of Y. pestis, suggesting that neutrophil interactions with Y. pestis may be important in bubonic plague pathogenesis. In the present study, we developed new tools allowing for intravital microscopy of Y. pestis in the dermis of an infected mouse after transmission by its natural route of infection, the bite of an infected flea. We found that uninfected flea bites typically induced minimal neutrophil recruitment. The magnitude of neutrophil response to flea-transmitted Y. pestis varied considerably and appeared to correspond to the number of bacteria deposited at the bite site. Macrophages migrated towards flea bite sites and interacted with small numbers of flea-transmitted bacteria. Consistent with a previous study, we observed minimal interaction between Y. pestis and dendritic cells; however, dendritic cells did consistently migrate towards flea bite sites containing Y. pestis. Interestingly, we often recovered viable Y. pestis from the draining lymph node (dLN) 1 h after flea feeding, indicating that the migration of bacteria from the dermis to the dLN may be more rapid than previously reported. Overall, the innate cellular host responses to flea-transmitted Y. pestis differed from and were more variable than responses to needle-inoculated bacteria. This work highlights the importance of studying the interactions between fleas, Y. pestis and the mammalian host to gain a better understanding of the early events in plague pathogenesis.

Yersinia versus host immunity: how a pathogen evades or triggers a protective response

“…Intravital imaging of immune cell responses following intradermal [19] or flea-transmitted [20] Y. pestis infection in mice reveal neutrophils as the predominant cell population associated with the bacteria. However, depletion of neutrophils using an anti-GR1 antibody does not appear to alter dissemination of Y. pestis in an intradermal mouse model of infection [19], nor does depletion of neutrophils using a Ly6G antibody alter bacterial colonization during pneumonic plague [21].…”

A Deadly Path: Bacterial Spread During Bubonic Plague

“…Y. pestis is detected in the dLN minutes after ID inoculation [4, 12]. Phagocytes reach LNs in hours, not minutes.…”

Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

“…More recently, several groups have begun to focus on the interaction between the bacteria and specific host cell types. It has been shown that the bacteria can survive and replicate in both macrophages and neutrophils (7,8) and that they can disseminate to the draining lymph node nearest the site of flea bite within an hour (9). However, relatively few studies have investigated host factors and responses that may confer resistance to infection.…”