The open immunology journal最新文献

Fungal sensitization in patients with asthma often indicates an unusual disease course in which traditional asthma treatments have little effect and in which morbidity is particularly severe. Airway hyperresponsiveness (AHR), inflammatory infiltrates, smooth muscle hyperplasia, and irreversible fibrotic remodeling of the bronchial architecture are features of allergic fungal asthma. The systemic production of IgE has long been associated with the immunopathogenesis of allergic asthma; however, the role of B lymphocytes and their products in the response to fungal allergens remains unclear. In the present study, we hypothesize that B lymphocytes are recruited to the allergic lung to impact the allergic response. Using a murine fungal aeroallergen model to mimic the human syndrome, we characterized the B cell population in the lung after fungal challenge and found that CD19(+)CD23(+) B2 lymphocyte numbers are increased in the allergic lung in a dynamic process. IgA, IgG(2a), and IgE were prominent in the serum and bronchoalveolar lavage fluid of allergic animals. It was evident that a tissue-centric production of these antibodies was possible. IgA-, IgG-, and IgE-producing cells from the allergic lung were identified by flow cytometry and immunohistochemistry. This study shows for the first time that CD19(+)CD23(+) B2 lymphocyte numbers change in the lung in a dynamic process after inhalation of fungal conidia and their increase has a significant impact on the Ab production in the pulmonary compartment in the context of fungal allergy.

We have shown that respiratory viral infections drive allergic disease through dendritic cells, whether gastrointestinal viruses induce allergies is not known. Norovirus infections are a major cause of gastroenteritis in humans. We used murine norovirus (MNV) to explore the effect of MNV infection on gastrointestinal conventional DCs (cDCs) and plasmacytoid DCs (pDCs). MNV infection induced disparate effects on cDCs and pDCs in lymphoid tissues of the small intestine and draining mesenteric lymph nodes. FcεRI was transiently expressed on lamina propria cDCs, but not on pDCs. In addition, feeding ovalbumin during the viral infection led to a modest, brief induction of anti-ovalbumin IgE. Together, these data suggest that like with a respiratory viral infection, an intestinal viral infection may be sufficient to induce changes in DCs and the generation of food-specific IgE. Whether this represents a novel mechanism of food allergy remains to be determined.

Mounting evidence suggests fibromyalgia (FM) symptoms are influenced by dysfunction of the hypothalamic-pituitary-hormonal axes (HPHA) and the immune response system. The predominant FM symptoms of widespread pain, fatigue, sleep disturbance, depression, stiffness and exercise intolerance are related to abnormal levels of growth hormone (GH) and are reminiscent of "sickness behavior"; a syndrome initiated by the production of pro-inflammatory cytokines in response to various stressors. Cognizant of the reciprocal relationship between HPHA activity and the immune response system, we hypothesized that serum cytokine levels and FM symptom severity would be higher in FM patients with defective growth hormone response to exhaustive exercise compared to those without. Outpatients with FM (n = 165) underwent a Modified Balke Treadmill Protocol and GH response to exhaustive exercise was measured in peripheral blood samples. Levels of IL-1α, IL-1β, IL-1RA, IL-6, IL-8, IL-10, and TNF-α were measured from stored serum on a subset of 24 participants (12 with and 12 without normal GH response to exhaustive exercise). FM symptom severity was assessed using the Fibromyalgia Impact Questionnaire (FIQ), number of tender points and cumulative myalgic scores. GH dysfunction was associated with increased pain scores on the FIQ (p = 0.024), a greater number of tender points (p = 0.014), higher myalgic scores (p = 0.001) and higher pre-exercise levels of inflammatory cytokines IL-1α (p = 0.021), IL-6 (p = 0.012), and IL-8 (p = 0.004). These results suggest that a defective growth hormone response to exercise may be associated with increased levels of blood cytokines and pain severity in FM patients.

Cigarette smoke (CS) exposure is known to increase infection rates, but the mechanisms are not well understood. These studies tested the hypothesis that CS exposure would impair antimicrobial activity of apical conditioned media from human airway (BEAS-2B) cultures by reducing induction and release of the antimicrobial peptide CCL20. BEAS-2B cultures were exposed to CS extract and assayed for temporal and physical characteristics of release as well as for antimicrobial activity. E. coli were exposed to Beas-2B-conditioned media (BCM) and subsequent bacterial colonies were enumerated. In time course studies TLR-agonist-induced CCL20 transcription and release were rapid, of short duration and release was consistently targeted to the apical/luminal compartment. Cells treated with CS extract had diminished release of CCL20 under both constitutive and toll-like receptor (TLR) agonist stimulating conditions. Exposure of the cells to CS significantly reduced the antimicrobial activity in BCM and neutralizing antibodies to CCL20 brought antibacterial activity back to baseline levels demonstrating that antimicrobial activity in this culture system was primarily attributable to CCL20. These studies add to the understanding of CCL20 as a mucosal antimicrobial and improve insight into a likely mechanism linking infection to CS exposure.

We have recently devised a culture method that generates large numbers of eosinophils at high purity from unselected BALB/c mouse bone marrow progenitors [Dyer et al., 2008. J. Immunol. 181: 4004-9]. Here we present the extended scope of this approach, as we have used this method successfully to generate eosinophil cultures of virtually 100% purity from bone marrow from C57BL/6 mice, and from TLR2, TLR3, TLR7 and TLR9-gene-deleted mouse strains on the C57BL/6 background. Both wild-type and TLR3 gene-deleted bone marrow eosinophils (bmEos) are functional, releasing peroxidase in response to the secretogogue, platelet activating factor. We have also used this method to re-evaluate production of eosinophils in bone marrow cultures from ΔdblGATA mice, a strain that is eosinophil-deficient in vivo. Interestingly, bmEos can be detected in the ΔdblGATA cultures (5% of total cells at day 10), although ~80-fold fewer bmEos are detected in ΔdblGATA than in parallel wild-type (BALB/c) bone marrow cultures. Overall, we find that generation of large numbers of eosinophils at high purity from unselected bone marrow progenitors proceeds efficiently in a variety of wild-type and gene-deleted strains, and as such this approach shows promise as a universal method for the study of eosinophil structure and function.

HSV-2 is a highly successful human pathogen with a remarkable ability to elude immune detection or counter the innate and adaptive immune response through the production of viral-encoded proteins. In response to infection, resident cells secrete soluble factors including chemokines that mobilize and guide leukocytes including T and NK cells, neutrophils, and monocytes to sites of infection. While there is built-in redundancy within the system, chemokines signal through specific membrane-bound receptors that act as antennae detailing a chemical pathway that will provide a means to locate and eliminate the viral insult. Within the central nervous system (CNS), the temporal and spatial expression of chemokines relative to leukocyte mobilization in response to HSV-2 infection has not been elucidated. This paper will review some of the chemokine/chemokine receptor candidates that appear critical to the host in viral resistance and clearance from the CNS and peripheral tissue using murine models of genital HSV-2 infection.