No abstract

Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with multiple human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Following primary infection, KSHV typically goes through a brief period of lytic replication prior to the establishment of latency. Plasmacytoid dendritic cells (pDCs) are the major producers of type 1 interferon (IFN), primarily in response to virus infection. Toll-like receptors (TLRs) are key components of the innate immune system, and they serve as pathogen recognition receptors that stimulate the host antiviral response. pDCs express exclusively TLR7 and TLR9, and it is through these TLRs that the type 1 interferon response is activated in pDCs. Currently, it is not known whether KSHV is recognized by pDCs and whether activation of pDCs occurs in response to KSHV infection. We now report evidence that KSHV can infect human pDCs and that pDCs are activated upon KSHV infection, as measured by upregulation of CD83 and CD86 and by IFN-␣ secretion. We further show that induction of IFN-␣ occurs through activation of TLR9 signaling and that a TLR9 inhibitor diminishes the production and secretion of IFN-␣ by KSHV-infected pDCs.

Objective. To evaluate the validity and acceptability of at-home self-collection to test for high-risk human papillomavirus (HPV) and sexually transmitted infections(STIs) among women overdue for cervical cancer screening by national guidelines. Methods. Low-income, infrequently screened women were recruited from the general population in North Carolina to participate in an observational study. Participants provided two self-collected cervico-vaginal samples (one at home and one in the clinic), and a clinician-collected cervical sample. Samples were tested for high-risk HPV, Chlamydia trachomatis(C. trachomatis), Neisseria gonorrhoeae(N. gonorrhoeae), Trichomonas vaginalis(TV), and Mycoplasma genitalium(M. genitalium). Cervical samples were also tested by liquid-based cytology. Results. Overall, 193 women had conclusive high-risk HPV results for all three samples and cytology results. Prevalence of high-risk HPV within self-home samples (12.4%) was not different from that within clinician samples (11.4%; p = 0.79) and to that within self-clinic samples (15.5%; p = 0.21) Positivity for high-risk HPV in all sample types increased with increasing grades of cervical abnormality (p<0.001). Self-home samples detected high-risk HPV in all identified cases of HSIL and of CIN2+. Detection was comparable across sample types for TV(range: 10.2%−10.8%), M. genitalium (3.3%−5.5%), C. trachomatis(1.1%−2.1%), and N. gonorrhoeae (0%−0.5%). Kappa values between sample types ranged from 0.56–0.66 for high-risk HPV, 0.86–0.91 for TV, and 0.65–0.83 for M. genitalium. Most participants reported no difficulty understanding self-collection instructions(93.6%), and were willing to use self-collection in the future(96.3%). Discussion: Mail-based, at-home self-collection for high-risk HPV and STI detection was valid and well-accepted among infrequently screened women in our study. These findings support the future use of high-risk HPV self-collection to increase cervical cancer screening rates among higher-risk women in the United States.