Aspergillus fumigatus in Poultry

Aspergillus fumigatus remains a major respiratory pathogen in birds. In poultry, infection by A. fumigatus may induce significant economic losses particularly in turkey production. A. fumigatus develops and sporulates easily in poor quality bedding or contaminated feedstuffs in indoor farm environments. Inadequate ventilation and dusty conditions increase the risk of bird exposure to aerosolized spores. Acute cases are seen in young animals following inhalation of spores, causing high morbidity and mortality. The chronic form affects older birds and looks more sporadic. The respiratory tract is the primary site of A. fumigatus development leading to severe respiratory distress and associated granulomatous airsacculitis and pneumonia. Treatments for infected poultry are nonexistent; therefore, prevention is the only way to protect poultry. Development of avian models of aspergillosis may improve our understanding of its pathogenesis, which remains poorly understood

Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms

<p>Abstract</p> <p>Background</p> <p><it>Aspergillus fumigatus</it>, a saprophytic mould, is responsible for life-threatening, invasive pulmonary diseases in immunocompromised hosts. The role of the airway epithelium involves a complex interaction with the inhaled pathogen. Antimicrobial peptides with direct antifungal and chemotactic activities may boost antifungal immune response.</p> <p>Results</p> <p>The inducible expression of defensins by human bronchial epithelial 16HBE cells and A549 pneumocyte cells exposed to <it>A. fumigatus </it>was investigated. Using RT-PCR and real time PCR, we showed an activation of hBD2 and hBD9 defensin genes: the expression was higher in cells exposed to swollen conidia (SC), compared to resting conidia (RC) or hyphal fragments (HF). The kinetics of defensin expression was different for each one, evoking a putative distinct function for each investigated defensin. The decrease of defensin expression in the presence of heat-inactivated serum indicated a possible link between defensins and the proteins of the host complement system. The presence of defensin peptide hBD2 was revealed using immunofluorescence that showed a punctual cytoplasmic and perinuclear staining. Quantification of the cells stained with anti hBD2 antibody demonstrated that SC induced a greater number of cells that synthesized hBD2, compared to RC or HF. Labelling of the cells with anti-hBD-2 antibody showed a positive immunofluorescence signal around RC or SC in contrast to HF. This suggests co-localisation of hBD2 and digested conidia. The HBD2 level was highest in the supernatants of cells exposed to SC, as was determined by sandwich ELISA. Experiments using neutralising anti-interleukine-1β antibody reflect the autocrine mechanism of defensin expression induced by SC. Investigation of defensin expression at transcriptional and post-transcriptional levels demonstrated the requirement of transcription as well as new protein synthesis during <it>A. fumigatus </it>defensin induction. Finally, induced defensin expression in primary culture of human respiratory cells exposed to <it>A. fumigatus </it>points to the biological significance of described phenomena.</p> <p>Conclusion</p> <p>Our findings provide evidence that respiratory epithelium might play an important role in the immune response during <it>Aspergillus </it>infection. Understanding the mechanisms of regulation of defensin expression may thus lead to new approaches that could enhance expression of antimicrobial peptides for potential therapeutic use during aspergillosis treatment.</p

Distribution tissulaire d'une molécule de classe II du BoLA distincte de BoLA-DR et -DQ

International audienceThis study was designed to investigate the lymphoid tissue distribution of a new BoLA class II molecule defined by a unique monoclonal antibody H42A. We immunostained various lymphoid organs of 4-month-old Holstein calves with this monoclonal antibody and compared its tissue distribution to the BoLA-DR and BoLA-DQ expressions. Our results demonstrate a unique tissue distribution of the H42A-defined molecules, restricted to epithelial cells of the thymic medulla but extending in the periphery to the different cells involved in antigen presentation (B-cells, macrophages and dendritic cells). The peculiar distribution of this new BoLA class II molecule suggests that it has a specific function

Feeding heated soyabean flour increases the density of B and T lymphocytes in the small intestine of calves.

International audienceThe effect of dietary antigens on the gut morphology and density of immune cells was studied in preruminant calves fed milk substitutes containing skim milk powder (SMP), non-antigenic hydrolysed soya protein isolate (HSPI) or antigenic heated soyabean flour (HSF) as their main protein source for 3 months. The height and perimeter of proximal jejunum villi were highest in the calves fed SMP and lowest in those fed HSF (P P P P P P < 0.01)

Histopathological changes in lymph nodes of cats experimentally infected with the feline immunodeficiency virus (FIV)

International audienceTwelve specific-pathogen-free (SPF) kittens aged 8-12 weeks were serially infected in pairs every 6 weeks, by the intraperitoneal route, with the feline immunodeficiency virus (FIV). Three additional SPF kittens were kept as controls. The infected animals were killed 10 weeks after inoculation, during the primary phase of the FIV infection. Generalized lymphadenopathy (GL) was observed in the first three pairs of cats. All lymph nodes examined from the 12 infected cats showed histological changes. These included severe follicular hyperplasia with hyperactive follicular centres (FCs) which were either (1) naked, (2) infiltrated by lymphocytes, (3) seen to contain islets of lymphocytic mantle cells, or (4) disrupted by lymphocytes. The presence of both CD4+ and CD8+ T lymphocytes was demonstrated in the FCs immunocytochemically. The distribution of CD4 lymphocytes resembled that in control lymph nodes, but the CD8 cells were increased in number and either scattered or clustered in the follicles. In addition, varying degrees of interfollicular proliferation and medullary plasmacytosis were observed in the lymph nodes. These findings, which were common to all infected animals, represented distinct prodromal manifestations of FIV infection. The changes in lymphocyte subpopulation distribution observed in early FIV infection were reminiscent of findings encountered in human immunodeficiency virus (HIV) infection and reinforce the suggestion that FIV infection is an appropriate model for the study of HIV pathogenesi

Histopathological changes in lymph nodes of cats experimentally infected with the feline immunodeficiency virus (FIV)

International audienceTwelve specific-pathogen-free (SPF) kittens aged 8-12 weeks were serially infected in pairs every 6 weeks, by the intraperitoneal route, with the feline immunodeficiency virus (FIV). Three additional SPF kittens were kept as controls. The infected animals were killed 10 weeks after inoculation, during the primary phase of the FIV infection. Generalized lymphadenopathy (GL) was observed in the first three pairs of cats. All lymph nodes examined from the 12 infected cats showed histological changes. These included severe follicular hyperplasia with hyperactive follicular centres (FCs) which were either (1) naked, (2) infiltrated by lymphocytes, (3) seen to contain islets of lymphocytic mantle cells, or (4) disrupted by lymphocytes. The presence of both CD4+ and CD8+ T lymphocytes was demonstrated in the FCs immunocytochemically. The distribution of CD4 lymphocytes resembled that in control lymph nodes, but the CD8 cells were increased in number and either scattered or clustered in the follicles. In addition, varying degrees of interfollicular proliferation and medullary plasmacytosis were observed in the lymph nodes. These findings, which were common to all infected animals, represented distinct prodromal manifestations of FIV infection. The changes in lymphocyte subpopulation distribution observed in early FIV infection were reminiscent of findings encountered in human immunodeficiency virus (HIV) infection and reinforce the suggestion that FIV infection is an appropriate model for the study of HIV pathogenesi

Distribution tissulaire d'une molécule de classe II du BoLA distincte de BoLA-DR et -DQ

International audienceThis study was designed to investigate the lymphoid tissue distribution of a new BoLA class II molecule defined by a unique monoclonal antibody H42A. We immunostained various lymphoid organs of 4-month-old Holstein calves with this monoclonal antibody and compared its tissue distribution to the BoLA-DR and BoLA-DQ expressions. Our results demonstrate a unique tissue distribution of the H42A-defined molecules, restricted to epithelial cells of the thymic medulla but extending in the periphery to the different cells involved in antigen presentation (B-cells, macrophages and dendritic cells). The peculiar distribution of this new BoLA class II molecule suggests that it has a specific function

Susceptibility of mice to invasive aspergillosis correlates with delayed cell influx into the lungs

International audienceP>Ubiquitous fungus Aspergillus fumigatus (A. fumigatus) is involved in invasive pulmonary aspergillosis (IPA), a frequent infection in immunocompromized patients. Genetic differences are likely to play a role predisposing to IPA. This study was aimed to compare six genetically different mouse strains in their susceptibility to IPA and to determine possible mechanisms involved in the pathogenesis of this infection. Immunosuppressed BALB/c and C57BL/6 mice infected with A. fumigatus conidia were more resistant to IPA than DBA/1, DBA/2, CBA, and A/Sn strains. Phagocytosis of A. fumigatus conidia by blood polymorphonuclear neutrophils (PMN) or bone marrow derived dendritic cells showed no difference between strains. All IPA susceptible strains demonstrated decreased PMN influx into the lungs during infection compared with resistant strains. Flow cytometry analysis of the composition of lung infiltrating cells showed that IPA susceptible mice had a decreased number of phagocytes before the infection. After infection the numbers of Gr-1(+)CD11b(+) PMN cells in the lungs of immunosuppressed mice increased from 10-20% to 50-60% while the percentage of CD11(+)F4/80(+) resident macrophages was unchanged. Among susceptible strains DBA/2 and A/Sn have a defect in C5 component of complement. Injection of normal serum into complement deficient but not into complement sufficient CBA or DBA/1 mice significantly improved their survival. We showed that complement replacement significantly increased PMN homing to the lungs of complement deficient mice. Thus, defect in complement system can predispose to IPA. Our results demonstrated that early influx of PMN into the lungs of mice is important for the resistance to IPA

Lymphoid activation : a confounding factor in AIDS vaccine development ?

International audienceIn a previous vaccination trial, inoculation of env gene DNA failed to elicit a detectable antibody response, yet accelerated virus dissemination in most immunized cats following challenge with feline immunodeficiency virus. This result raised the possibility that cell-mediated immune responses had given rise to immune-mediated enhancement of infection. Since high-level replication of immunodeficiency viruses in lymphocytes requires cellular activation, antigen-specific responses or non-specific polyclonal activation may have increased the frequency of optimal target cells. In the present DNA vaccination trial, although designed so as to minimize non-specific polyclonal activation, immune-mediated enhancement was nonetheless observed in certain immunized cats. Moreover, rapid virus dissemination in vivo was associated with the presence of T-helper responses prior to challenge, and was linked to increased susceptibility of lymphocytes to ex vivo infection. Immune activation may thus be a confounding factor in vaccination against lentivirus infection, diminishing vaccine efficacy and giving rise to immune-mediated enhancement

Identification of Novel Zoonotic Activity of Bartonella spp., France

Certain Bartonella species are known to cause afebrile bacteremia in humans and other mammals, including B. quintana, the agent of trench fever, and B. henselae, the agent of cat scratch disease. Reports have indicated that animal-associated Bartonella species may cause paucisymptomatic bacteremia and endocarditis in humans. We identified potentially zoonotic strains from 6 Bartonella species in samples from patients who had chronic, subjective symptoms and who reported tick bites. Three strains were B. henselae and 3 were from other animal-associated Bartonella spp. (B. doshiae, B. schoenbuchensis, and B. tribocorum). Genomic analysis of the isolated strains revealed differences from previously sequenced Bartonella strains. Our investigation identifed 3 novel Bartonella spp. strains with human pathogenic potential and showed that Bartonella spp. may be the cause of undifferentiated chronic illness in humans who have been bitten by ticks