Mature CD11c+ cells are enhanced in hypersensitivity pneumonitis

Abstract

The present study verified the hypothesis that enhanced maturation of antigenpresenting CD11c+ cells could explain the viral-induced exacerbated immune response to Saccharopolyspora rectivirgula (SR), the main antigen responsible for farmer's lung, a classic form of hypersensitivity pneumonitis (HP). Four groups of mice were studied: group 1 received intranasal instillations of saline; group 2 received instillations of SR for 12 weeks; group 3 received instillations of saline and a single infection with Sendai virus on week 3; and group 4 received instillations of SR for 12 weeks with a single administration of Sendai virus on week 3. On week 13, mice were sacrificed and bronchoalveolar lavage was performed. Lungs were harvested, digested with enzymes, and CD11c + cells were analysed in flow cytometry with anti-CD11c, anti-CD86 and anti-major histocompatibility complex class II markers. Immunofluorescence studies were also performed with the same cell surface markers. Both flow cytometry and immunofluorescence results demonstrate that mature CD11c + cells are significantly enhanced in SR-challenged mice simultaneously infected with Sendai virus, compared with other groups. These CD11c + cells persist in the lung for 9 weeks after the virus infection. Maturation of CD11c + cells could explain, at least in part, the virus-induced increased immune response to SR antigens in this model of HP, but mechanisms have still to be elucidated.

Mycobacterial hypersensitivity pneumonitis requires TLR9–MyD88 in lung CD11b+ CD11c+ cells

“…Our results indicated that TLR9-MyD88 signalling in lung CD11b+ DCs contributes to the pathogenesis of HP that is ascribed to inhaled M. avium. These data were supported by previous studies, in which lung CD11c+ cells, MyD88 and MyD88-mediated protein kinase D1 were shown to be associated with the neutrophilic inflammatory response in a mouse farmer's lung model with S. rectivirgula exposure [41][42][43]. Thus, the results of the present and previous studies demonstrated that genetic deficiency of TLR2 represents no impact on HP-like reactions to M. avium and S. rectivirgula [43].…”

CD34 Is Required for Dendritic Cell Trafficking and Pathology in Murine Hypersensitivity Pneumonitis

“…Finally, there is experimental evidence to suggest that maturation of DCs via a viral infection can lead to an HP-prone, hyperresponsive lung environment (11,12), as viral infections before exposure to the SR antigen in mice leads to more severe HP (11).…”

“…To test the role of CD34 in the development of Th1/Th17 lung inflammatory disease, we used a well-described Farmer's lung model of HP (3,11,12,23). The development of pulmonary inflammation was first assessed through analysis of the BAL cellular content.…”

“…HP was induced as previously described (3,11,12,23) by injecting 50 ml of 4 mg/ml endotoxin-free SR antigen intranasally three times a week for 3 weeks. Four days after the last intranasal instillation, mice were anesthetized with ketamine/xylazine and blood was collected by cardiac puncture.…”

Impaired function of regulatory T-cells in hypersensitivity pneumonitis

“…We have previously reported that a viral infection could trigger an exacerbated immune response to S. rectivirgula antigen in a mouse model of HP [22]. In that viral-induced HP murine model, Sendai, a paramyxoviral infection, leads to dendritic cell maturation and upregulation of MHC class II and CD86 [23]. Indeed, some studies have shown that over expression of co-stimulatory molecules, such as MHC class II, CD80 and CD86, decreases the suppressive effects of Treg-cells and promotes effector T-cell activation [24].…”