T cell response kinetics determines neuroinfection outcomes during murine HSV infection

Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear. In this study, we show that vaginal infection of mice with HSV-1 leads to the rapid appearance of mature DCs in the draining lymph node, which is dependent on an early burst of NK cell-mediated IFN-γ production in the vagina that occurs after HSV-1 infection but not HSV-2 infection. Rapid DC maturation after HSV-1 infection, but not HSV-2 infection, correlates with the accelerated generation of a neuroprotective T cell response and early accumulation of IFN-γ-producing T cells at the site of infection. Depletion of T cells or loss of IFN-γ receptor (IFN-γR) expression in sensory neurons both lead to a marked loss of neuroprotection only during HSV-1, recapitulating a prominent feature of HSV-2 infection. Our experiments reveal key differences in host control of neuronal HSV-1 and HSV-2 infection after genital exposure of mice, and they define parameters of a successful immune response against genital herpes

Ritmo Learning Lab - Joomajam: A usage, attitude and image study on e-learning focused on application downloading in selected areas in Metro Manila

This study sought to examine the extent to which downloadable application can be utilized to heighten learning and bonding amongst pre-school children and parents. Further it aims to understand the short fall in sales of Joomajam despite the increase in its awareness over the course of a four (4) month campaign targeted at Moms of pre-school children and to recommend ways of increasing the sales. The research then draws attention to the fact that in Philippines as of to date, 22.6 million children are still engaged in traditional learning. Technology is quickly changing in every aspect of the society and yet, parents still adhere to the century-old idea that traditional learning is still the best method for their children. When parents do not utilize technology in improving their child\u27s learning, they neglect to see the benefits of the resources available today. Smartphones and tablets according to various health experts and pediatricians can either be beneficial to the user or detrimental to one\u27s health. But with lack of proof to bolster the claims of these health experts and also due to the fact that research on the impacts of using smartphone apps and tablets are still at its early stages, it left parents confused whether the exposure of smartphone and tablets can be good or bad to their children. As researchers for Ritmo Learning Lab, the group sought out what potential problems could have affected the sales. Further investigations revealed that there was no local e-Book store. This formed a gap in the local e-Book market by not providing a business platform anyone can easily access. Moreover, the image-bashing claims by health experts contributed to the uncertainty the eBooks or apps. These factors coupled with a target niche market made it difficult for Joomajam to realize sales in the first few months and it appeared to be the major causes for Joomajam\u27s shortcoming to reach its expected output. Joomajam needs to be flexible in terms of compatibility with other operating systems. The study confirms that almost half of the respondents interviewed (32 of 76) used educational applications. Although that is roughly one-third of our respondents, the study suggests that marketing in iOS alone will not be sufficient to make the company sustainable. The study evaluates and concludes that there are numerous naturally occurring segments that Joomajam can venture with, and gain market share. It is recommended that Joomajam: 1. take advantage and be more focused on the potential market of android users 2. endorse their products to pre-schools that have no prescribed applications 3. create tangible products for the market of non-android and non-iOS users

NK cell-derived extracellular granzyme B drives epithelial ulceration during HSV-2 genital infection

Summary: Genital herpes is characterized by recurrent episodes of epithelial blistering. The mechanisms causing this pathology are ill defined. Using a mouse model of vaginal herpes simplex virus 2 (HSV-2) infection, we show that interleukin-18 (IL-18) acts upon natural killer (NK) cells to promote accumulation of the serine protease granzyme B in the vagina, coinciding with vaginal epithelial ulceration. Genetic loss of granzyme B or therapeutic inhibition by a specific protease inhibitor reduces disease and restores epithelial integrity without altering viral control. Distinct effects of granzyme B and perforin deficiency on pathology indicates that granzyme B acts independent of its classic cytotoxic role. IL-18 and granzyme B are markedly elevated in human herpetic ulcers compared with non-herpetic ulcers, suggesting engagement of these pathways in HSV-infected patients. Our study reveals a role for granzyme B in destructing mucosal epithelium during HSV-2 infection, identifying a therapeutic target to augment treatment of genital herpes