Yersinia pestis and host macrophages: immunodeficiency of mouse macrophages induced by YscW

Abstract

Summary The virulence of the pathogenic Yersinia species depends on a plasmid‐encoded type III secretion system (T3SS) that transfers six Yersinia outer protein (Yop) effector proteins into the cytoplasm of eukaryotic cells, leading to disruption of host defence mechanisms. It is shown in this study that Yersinia pestis YscW, a protein of the T3SS injectisome, contributes to the induction of a deficiency in phagocytosis in host macrophages and a reduction in their antigen‐presenting capacity. A Y. pestis strain lacking yscW had no effect on uptake by host macrophages. In mice infected with wild‐type Y. pestis, the yscW mutant or a complement strain, immunodeficiency was observed in host macrophages compared with those from uninfected mice. However, the phagocytosis and antigen presenting capacities of macrophages infected by yscW mutant strain both in vivo and in vitro were significantly higher than those by wild type strain. Consistent with this finding, when YscW was expressed in the RAW264·7 macrophage cell line, phagocytosis and antigen‐presenting capacities were significantly lower than those of the control groups. These results indicate that Y. pestis YscW may directly induce immunodeficiency in murine macrophages by crippling their phagocytosis and antigen‐presenting capacities. These data provide evidences to Y. pestis pathogenesis that some proteins in T3SS injectisome, such as YscW protein, might play independent roles in disrupting host defense apart from their known functions.

Determination of sRNA Expressions by RNA-seq in Yersinia pestis Grown In Vitro and during Infection

“…pestis sRNA deletion mutants were constructed by λ-Red or suicide plasmid homologous combination systems as previously described [12,49]. For the λ-Red method, the sRNA deletion mutants were constructed by replacing the sRNA gene with the kan cassette.…”

New Role for FDA-Approved Drugs in Combating Antibiotic-Resistant Bacteria

“…During infection, Y. pestis preferentially targets host macrophages, as the organism is protected from contact with other immune components and acquires the ability to evade subsequent phagocytosis (23,24). Macrophages are key effectors of the host innate immune response to infection and intracellular survival and growth of Y. pestis, and since macrophages play a pivotal role in the pathogenesis of the plague (23,24,51), this in vitro model was well suited for our screening purposes. In total, 94 FDA-approved drugs were identified in our screen as being able to inhibit Y. pestis-induced macrophage cytotoxicity.…”

“…Although not an exact clinical correlate, macrophages are an essential component of innate immunity and the first line of defense for numerous infections, including those with the facultative intracellular pathogen Y. pestis (11,23,24), making this approach a rapid and effective way to identify lead therapeutic compounds for further studies in in vivo models. By in vitro screening, we reproducibly, through two independent experiments performed in duplicate, identified 94 drugs significantly effective at preventing macrophage cytotoxicity during Y. pestis infection.…”

IL-17A Produced by Neutrophils Protects against Pneumonic Plague through Orchestrating IFN-γ–Activated Macrophage Programming

“…Plague is one of the deadliest infectious diseases (1,41). The causative agent, Y. pestis, is a Gram-negative facultative bacterium that is naturally transmitted from rodents to humans by fleas (2).…”