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Mycobacterium tuberculosis subverts host immunity to proliferate within host tissues. Non-selective transient receptor potential (TRP) ion channels are involved in host responses and altered upon bacterial infections. Altered expression and localization of TRPV4 in macrophages upon virulent M. tuberculosis infection together with differential distribution of TRPV4 in human tuberculosis (TB) granulomas indicate a role of TRPV4 in TB. Compared with wild-type mice, Trpv4-deficient littermates showed transiently higher mycobacterial burden and reduced proinflammatory responses. In the absence of TRPV4, activation failed to render macrophages capable of controlling mycobacteria. Surprisingly, Trpv4-deficient mice were superior to wild-type ones in controlling M. tuberculosis infection in the chronic phase. Thus, Trpv4 is important in host responses to mycobacteria, although with opposite functions early versus late in infection. Ameliorated chronic infection in the absence of Trpv4 and its expression in human TB lesions indicate TRPV4 as putative target for host-directed therapy.Despite common consensus about the importance of planar cell polarity (PCP) proteins in tissue orientation, little is known about the mechanisms used by PCP proteins to promote planar polarization of cytoskeletons within individual cells. One PCP protein Fzd6 asymmetrically localizes to the apical cell membrane of multi-ciliated ependymal cells lining the lateral ventricular (LV) wall on the side that contacts cerebrospinal fluid flow. Individual ependymal cells have planar polarized microtubules that connect ciliary basal bodies (BBs) with the cell cortex of the Fzd side to coordinate cilia orientation. Here, we report that cytoplasmic dynein is anchored to the cell cortex of the Fzd side via an adapter protein Daple that regulates microtubule dynamics. Asymmetric localization of cortical dynein generates a pulling force on dynamic microtubules connected to BBs, which in turn orients BBs toward the Fzd side. This is required for coordinated cilia orientation on the LV wall.During collective cell migration, front cells tend to extend a predominant leading protrusion, which is rarely present in cells at the side or rear positions. Using Drosophila border cells (BCs) as a model system of collective migration, we revealed the presence of a supracellular actomyosin network at the peripheral surface of BC clusters. We demonstrated that the Myosin II-mediated mechanical tension as exerted by this peripheral supracellular network not only mediated cell-cell communication between leading BC and non-leading BCs but also restrained formation of prominent protrusions at non-leading BCs. Further analysis revealed that a cytoplasmic dendritic actin network that depends on the function of Arp2/3 complex interacted with the actomyosin network. Together, our data suggest that the outward pushing or protrusive force as generated from Arp2/3-dependent actin polymerization and the inward restraining force as produced from the supracellular actomyosin network together determine the collective and polarized morphology of migratory BCs.To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.Objectives In August 2016, a measles outbreak at Kansai International Airport was the first workplace measles outbreak since Japan was verified as having achieved measles-elimination status in March 2015. We investigated this outbreak with a focus on evaluating the ability of vaccinated individuals to transmit measles virus (MV). Methods We considered a case of laboratory-confirmed measles with onset between August 9 and September 29, 2016, among workers of Kansai International Airport. History of vaccination status with measles-containing vaccine (MCV) was confirmed by reviewing records. The potential sources of each MV infection were assessed by interviewing each infected worker about the clinical course of their infection and their behavioral history. read more Results Of 30 affected ground crews identified, 16 (53%) were vaccinated with ≥ 1 dose of MCV, 2 (7%) were unvaccinated, and 12 (40%) had an unknown vaccination status. The index case, a patient with classical measles with unknown vaccination status, presumably transmitted MV to all the subsequent 29 cases. The majority of patients (23, 77%; 15 vaccinated, 8 in unknown vaccination status) were diagnosed with modified measles due to mild illness. Modified measles were characterized clinically by signs of catarrh (4/23, 17%) in a few cases, with a median incubation period of 16 (range, 11-21) days. No onward transmission from vaccinated cases was suggested. An overseas traveler who visited the airport with measles symptoms was identified as the possible primary source of this outbreak. Conclusions The low MV transmission ability of vaccinated individuals was reaffirmed. Contact tracing of vaccinated modified measles cases can be limited to a person at high risk of infection (e.g., households, person with immunosuppression). To maintain measles-elimination status, completing two doses of MCV should be ensured, especially for international travelers and for those who are frequently exposed to these travelers, such as airport workers.
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