Background Healthy vaginal microbiome is dominated by Lactobacilli, which constitute a strong line of defense against vaginal diseases like Bacterial vaginosis (BV). Bacterial Vaginosis is a polymicrobial disease characterized by gradual replacement of predominant population of Lactobacillus with anaerobic uropathogens such as Gardnerella vaginalis (GV), Prevotella and Mobiluncus spp. Due to antibiotic resistance in these pathogens, Lactobacillus spp. have been given attention in the prophylaxis and prevention of infections such as, urinary tract infections, genital infections and BV. Current study describes role of L. reuteri in reducing BV in a GV induced BV murine model. In addition, immunomodulatory effects of L. reuteri were assessed by analyzing gene expression of in ammatory and anti-in ammatory markers by real time PCR in vaginal tissue. Methods Study was divided into two parts. In phase 1, two groups of mice were intravaginally administered with L. reuteri and GV at a dose of 1 x 10 6 CFUml-1 and 5 x 10 5 CFUml-1 respectively and their colonization was con rmed by re-isolation of these strains in vaginal washes. In phase 2, prophylactic e cacy of L. reuteri in GV induced BV mice model were observed by considering clinical scoring, re-isolation frequency, bacterial load, change in epithelium of vaginal tissue and tissue in ammatory and anti-in ammatory markers. Results A signi cant reduction in clinical scores and re-isolation frequency was noticed in GV challenged pre-L. reuteri colonized animals (prophylactic group). On 10 th day, L. reuteri restricted the growth of GV

Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20–40% of CF patients and are of unclear clinical significance. In this study, we demonstrate that CF transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftrtm1Unc-TgN(fatty acid-binding protein)CFTR) and mutant (ΔF508) mice develop profound lung inflammation in response to Aspergillus fumigatus hyphal Ag exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in serum. In contrast, CFTR deficiency does not promote a Th1 immune response. Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells.

Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well known triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here, we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4 independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response and potentially impact the development of allergic airway disease to environmental fungal antigens.Key words: Cytokines . Eosinophils . Immune responses . Lung inflammation . Th cells IntroductionAllergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance (R n ) [1][2][3]. This response results from antigen-specific Th2 cell activation characterized by IL-4, IL-5 and IL-13 production [4]. IL-4 and IL-5 stimulate eosinophil maturation and activation while IL-13 is an important mediator of mucus production [4,5]. Among inhaled allergens that can trigger this type of immune response are a number of fungal species [6]. These agents can stimulate allergic inflammation without causing active infection in the immunocompetent host [6][7][8]. It is unclear why airway 776exposure to fungal antigens leads to a Th2 immune response but may result from specific antigenic determinants of the fungi that preferentially stimulate Th2 responses. However, CD4 T cells from mice with transgenic T-cell receptors specific for a particular Aspergillus antigen differentiate ex vivo into IFN-g-producing Th1 cells rather than Th2 cells [9]. Alternatively, it could be the lung environment with its costimulatory cytokine milieu that predisposes to a Th2 immune response to fungal antigens. Interestingly, not all individuals develop allergic airway inflammation in response to inhaled fungal allergens despite ubiquitous exposure [10]. The 'hygiene hypothesis' proposes that lung exposure to certain bacterial components (e.g. CpG DNA) could modulate the Th2immune response [11][12][13]. Thus, CD4 T cell immune response to specific protein antigens could be modulated by exposure to bacterial microbial products.We h...

Indoleamine 2,3-dioxygenase (IDO) suppresses the functions of CD4 1 T cells through its ability to metabolize the essential amino acid tryptophan. Although the activity of IDO is required for the immunosuppression of allergic airway disease by the Toll-LikeReceptor 9 (TLR9) agonist, oligonucleotides comprised of cytosine and guanine nucleotides linked by phosphodiester bonds (CpG) DNA, it is unclear whether IDO expression by resident lung epithelial cells is sufficient to elicit these effects. Therefore, we created a transgenic mouse inducibly overexpressing IDO within nonciliated airway epithelial cells. Upon inhalation of formalin-fixed Aspergillus fumigatus hyphal antigens, the overexpression of IDO from airway epithelial cells of these mice reduced the number of CD4 1 T cells within the inflamed lung and impaired the capacity of antigen-specific splenic CD4 1 effector T cells to secrete the cytokines IL-4, IL-5, IL-13, and IFN-g. Despite these effects, allergic airway disease pathology was largely unaffected in mice expressing IDO in airway epithelium. In support of the concept that dendritic cells are the major cell type contributing to the IDO-inducing effects of CpG DNA, mice expressing TLR9 only in the airway epithelium did not augment IDO expression subsequent to the administration of CpG DNA. Furthermore, the systemic depletion of CD11c 1 cells rendered mice incapable of CpG DNA-induced IDO expression. Our results demonstrate that an overexpression of IDO within the airway epithelium represents a novel mechanism by which the number of CD4 1 T cells recruited to the lung and their capacity to produce cytokines can be diminished in a model of allergic airway disease, and these results also highlight the critical role of dendritic cells in the antiasthmatic effects of IDO induction by CpG DNA.

Activation of Th2 CD4+ T cells is necessary and sufficient to elicit allergic airway disease, a mouse model with many features of human allergic asthma. Effectively controlling the activities of these cells could be a panacea for asthma therapy. Blood-feeding parasites have devised remarkable strategies to effectively evade the immune response. For example, ticks such as Ixodes scapularis, which must remain on the host for up to 7 days to feed to repletion, secrete immunosuppressive proteins. Included among these proteins is the 15-kDa salivary protein Salp15, which inhibits T cell activation and IL-2 production. Our objective for these studies was to evaluate the T cell inhibitory properties of Salp15 in a mouse model of allergic asthma. BALB/cJ mice were Ag sensitized by i.p. injection of OVA in aluminum hydroxide, with or without 50 μg of Salp15, on days 0 and 7. All mice were challenged with aerosolized OVA on days 14–16 and were studied on day 18. Compared with control mice sensitized with Ag, mice sensitized with Ag and Salp15 displayed significantly reduced airway hyperresponsiveness, eosinophilia, Ag-specific IgG1 and IgE, mucus cell metaplasia, and Th2 cytokine secretion in vivo and by CD4+ T cells restimulated with Ag in vitro. Our results demonstrate that Salp15 can effectively prevent the generation of a Th2 immune response and the development of experimental asthma. These studies, and those of others, support the notion that a lack of ectoparasitism may contribute to the increasing prevalence of allergic asthma.