Articles of Significant Interest Selected from This Issue by the Editors

Host Factor Dynamics at the Entry Site of Shigella flexneri during Epithelial Cell Invasion

Shigella flexneri, the causative agent of bacillary dysentery, triggers its uptake into nonphagocytic epithelial cells, resulting in cytoskeletal rearrangements at the entry site. Upon entry, the invading bacterium escapes from the endocytic vacuole to replicate within the cytoplasm. Ehsani et al. (p. 2548–2557) investigated the spatiotemporal dynamics of host factors at the bacterial entry site and during vacuolar escape. This work showed that (i) host factors are simultaneously recruited to the forming vacuole, (ii) host factors are sequentially dispersed from the rupturing vacuole, and (iii) the bacterial effector IpgB1 accelerates entry but not vacuolar progression or rupture.

Heterogeneity of Immature Myeloid Cells in the Host Response to Tularemia

Accumulation of Gr-1⁺ CD11b⁺ cells has been linked to immunosuppression under diverse pathological conditions, including infection and cancer. Rasmussen et al. (p. 2371–2381) demonstrate that Gr-1⁺ CD11b⁺ cells are the largest population of cells present in spleens of mice infected with Francisella tularensis and that these cells can be further subdivided into mononuclear CD11b⁺ Ly6C^hi Ly6G⁻ cells and polymorphonuclear CD11b⁺ Ly6C^int Ly6G⁺ cells. While the CD11b⁺ Ly6C^hi Ly6G⁻ cells inhibited proliferation of T cells via a nitric oxide-dependent pathway, the large presence of Gr-1⁺ CD11b⁺ cells in mice that survived infection also suggests a role for these cells in the protective host response to tularemia.

Brucella abortus Takes Control of Bone Dynamics

Osteoarticular brucellosis is the most common presentation of the active disease in humans. Although the clinical aspects of this form of the disease have been widely described, the molecular pathogenic mechanisms have been partially described only recently. Work by Scian et al. (p. 2333–2345) described the modifications that occur in osteoblast metabolism when these cells are infected by Brucella abortus and how this response inhibits osteoblasts differentiation and function, leading to bone loss. They demonstrate that B. abortus infection induces upregulation of RANKL expression and osteoblast apoptosis and inhibits the deposition of organic and mineral bone matrices, contributing to bone loss and damage.

Not Just Myeloperoxidase: Vascular Peroxidase 1 Is Capable of Generating Hypochlorous Acid in Plasma

Animal heme-containing peroxidases mediate host defense functions via generation of hypohalous acids. Until now, myeloperoxidase (MPO) was considered unique in its ability to utilize chloride to generate the highly microbicidal species hypochlorous acid (HOCl) under physiologic conditions. However, MPO-deficient individuals are not inordinately susceptible to infections. Li et al. (p. 2528–2537) demonstrate that vascular peroxidase 1 (VPO1), a newly discovered peroxidase in plasma, is capable of generating HOCl and mediates microbial killing. This work supports physiological roles of VPO1 in host defense and maintaining sterility of circulating plasma. The absence of a phenotype in MPO-deficient individuals may be a result of a redundant role of VPO1.

Surfactant D Is a Risk Factor for Cryptococcosis

Cryptococcosis is generally considered to be initiated by inhalation of spores or yeasts, and therefore, initial innate immune mechanisms are considered to be important. In this study, Guenes-Boyer et al. (p. 2444–2453) hypothesized that surfactant D would protect the mammalian host from cryptococcal invasion, as it protects other microbes. However, experimental results favored the opposite conclusion, supporting the fact that Cryptococcus neoformans instead coopts this generally protective mechanism to aid in its production of disease. This study could have implications on our understanding of host susceptibility to cryptococcal disease.