Secondary bacterial coinfections following influenza virus pose a serious threat to human health. Therefore, it is of significant clinical relevance understand the immunological causes this increased susceptibility. Influenza-induced alterations in alveolar macrophages (AMs) have been shown be major underlying cause susceptibility superinfection. However, mechanisms responsible for remain under debate, specifically terms whether AMs are depleted response infection or maintained...

We have recently shown that intranasal (i.n.) administration of γ-irradiated A/PR/8 [A/Puerto Rico/8/34 (H1N1)] protects mice against lethal avian influenza A/Vietnam/1203/2004 (H5N1) and other heterosubtypic A infections. Here, we used γ-irradiated, formalin- UV-inactivated A/PC [A/Port Chalmers/1/73 (H3N2)] virus preparations compared their ability to induce both homologous protective immunity. Our data show that, in contrast i.n. vaccination with or virus, the present commercially...

We previously demonstrated that a single dose of nonadjuvanted intranasal gamma-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian strain. investigated the mechanism behind observed cross-protection to define which arms adaptive immune response are involved mediating this protection. Studies gene knockout showed cross-protective immunity be mediated mainly by T cells dependent on...

Background Influenza A (flu) virus causes significant morbidity and mortality worldwide, current vaccines require annual updating to protect against the rapidly arising antigenic variations due shift drift. In fact, subunit or split flu rely exclusively on antibody responses for protection do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between strains. We have previously reported that γ-ray inactivated can Tc responses. Methodology/Principal Finding Here, we...

Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists directly demonstrate the impact of asthma on susceptibility infection. Using mouse model, we now report that asthmatic mice are actually significantly more resistant lethal virus challenge. Notably, observed increased resistance was not attributable enhanced viral clearance, but instead, due reduced lung inflammation. Asthmatic exhibited cytokine storm, as well total protein levels and...

Streptococcus pneumoniae (Spn) is a common pathogen causing secondary bacterial infection following influenza, which leads to severe morbidity and mortality during seasonal pandemic influenza. Therefore, there an urgent need develop vaccines that prevent post-influenza pneumonia. Here, improved Yersinia pseudotuberculosis strain (designated as YptbS46) possessing Asd+ plasmid pSMV92 could synthesize high amounts of the Spn pneumococcal surface protein A (PspA) antigen monophosphoryl lipid...

Background. Secondary bacterial infections following influenza represent a major cause of mortality in the human population, which, turn, has led to call for stockpiling vaccines pandemic preparedness.

Abstract The effects of aging on innate immunity and the resulting impacts immunosenescence remain poorly understood. Here, we report that induces compartmentalized changes to development function group 2 lymphoid cells (ILC2), an ILC subset implicated in pulmonary homeostasis tissue repair. Aging enhances bone marrow early ILC2 through Notch signaling, but newly generated circulating are unable settle lungs replenish concomitantly declining mature lung pool aged mice. Aged...

Neuropsychological data in primates demonstrated a pivotal role of the hippocampal formation (HF) and parahippocampal gyrus (PH) navigation episodic memory. To investigate HF PH neurons environmental scaling primates, we recorded neuronal activities monkey during virtual (VN) pointer translocation (PT) tasks. The monkeys had to navigate within three differently sized spaces with same spatial cues (VN task) or move on screen (PT by manipulating joystick receive reward. Of 234 neurons, 170 61...

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen associated with nosocomial pneumonia and an increasing threat for severe community-acquired pneumonia. We have now investigated the role of interleukin-12 (IL-12) in protective immunity against lung infection MRSA. The importance IL-12 protection from pulmonary MRSA was demonstrated by finding that IL-12p35-deficient mice had lower survival rate, higher bacterial burdens spleen, decreased expression interferon gamma...

Francisella tularensis causes lethal pneumonia following infection of the lungs by targeting macrophages for intracellular replication; however, stimulated with interferon gamma (IFN-γ) can resist in vitro We therefore hypothesized that protective effect IFN-γ against F. tularensisin vivo requires receptive to stimulation. found lethality pulmonary LVS was exacerbated under conditions alveolar macrophage depletion and mice a macrophage-specific defect signaling (termed insensitive [MIIG...

E-2078 ([N-methyl-Tyr1, N-methyl-Arg7, D-Leu8]dynorphin A (1-8) ethylamide) is a systematically active dynorphin analog. We examined the sites of action analgesia induced by systemic application compared with morphine in mice. When administered either intracerebroventricularly or intrathecally, produced maximal dose-dependent tail-pinch, tail-flick and formalin tests. Its peak effect was observed 15 min after both injections, contrasted slow (120 min) subcutaneous injection. The intrathecal...

Francisella tularensis, the causative agent of tularemia, is most deadly in pneumonic form; therefore, mucosal immunity an important first line defense against this pathogen. We have now evaluated lethality primary F. tularensis live vaccine strain (LVS) pulmonary infection mice that are defective IgA (IgA(-/-) mice), predominant Ig isotype. The results showed IgA(-/-) were more susceptible than IgA(+/+) to intranasal LVS infection, despite developing higher levels LVS-specific total, IgG,...

Interleukin-33 (IL-33) is a multifunctional cytokine that mediates type 2-dominated immune responses. In contrast, the role of IL-33 during viral vaccination, which often aims to induce 1 immunity, has not been fully investigated. Here, we examined effects on influenza vaccine We found intranasal coadministration with an inactivated virus increases efficacy against infection, only homologous strain but also heterologous strains, including 2009 H1N1 pandemic strain. Cross-protection was...

Background We have shown previously in mice, that infection with live viruses, including influenza/A and Semliki Forest virus (SFV), induces systemic partial activation of lymphocytes, characterized by cell surface expression CD69 CD86, but not CD25. This lymphocytes is mediated type-I interferons (IFN-I). Importantly, we γ-irradiated SFV does induce IFN-I the associated lymphocyte activation. Principal Findings Here report that, contrast to SFV, influenza A elicits vivo. Furthermore, show...

ABSTRACT Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected patients with asthma and chronic obstructive pulmonary (COPD), a condition similar asthma, protects against the development of complicated pneumonia. To clarify effects on subsequent susceptibility infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced mice followed by...

During the previous influenza seasons, between 2010 and 2016, live attenuated vaccine (LAIV) provided variable efficacy against in U.S., causing recommendation use of LAIV. In striking contrast, pre-clinical studies have repeatedly demonstrated superior LAIV mismatched viruses, compared to inactivated vaccines (IIV). This disparity reported efficacies clinical may part be explained by limitations animal models influenza. particular, absence pre-existing immunity has recently emerged as a...

Asthma was the most common comorbidity observed among patients hospitalized with influenza A virus during 2009 pandemic. However, little remains known about how asthmatic phenotype influences protective immune responses against respiratory viral pathogens. Using ovalbumin-induced allergic lung inflammation model, we found that mice, unlike nonasthmatic were highly susceptible to secondary heterologous challenge. While primary infection generated memory homologous challenge in both and full...

Many currently available inactivated vaccines require "adjuvants" to maximize the protective immune responses generated against antigens of interest. Recent studies in mice with gamma-irradiated influenza A virus (γ-FLU) have shown its superior efficacy compared other forms FLU and ability induce both potent interferon type-I (IFN-I) IFN-I-associated partial lymphocyte activation. Commonly, IFN-I induced by adjuvants, combined vaccine preparations, been effectively enhance immunogenicity...

Fatal outcomes following influenza infection are often associated with secondary bacterial infections. Allergic airway disease (AAD) is known to influence severe complications from respiratory infections, and yet the mechanistic effect of AAD on virus-Streptococcus pneumoniae coinfection has not been investigated previously. We examined impact host susceptibility viral-bacterial coinfections. report that improved survival during when challenge occurred 1 week after AAD. Counterintuitively,...