Christopher Blair

Role of Type 1 T Helper Cells in the Resolution of Acute Streptococcus pneumoniae Sinusitis: A Mouse Model

BACKGROUND We examined the importance of the adaptive and innate immune responses in the resolution of an acute bacterial sinus infection in mice. METHODS Recombinase-activating gene knockout (RAG-1(-/-)) (no lymphocytes) and C57BL/6 (wild-type) mice were infected with Streptococcus pneumoniae. For determination of the cell type involved, lymphocytes from mice were adoptively transferred into RAG-1(-/-), C57BL/6 (all lymphocytes), B cell-deficient, and T cell-deficient mice. The degree of infection and inflammation was determined by quantification of S. pneumoniae from nasal lavage and analysis of sinus tissue, respectively. RESULTS In C57BL/6 mice, both the infection and inflammation resolved in 21 days, whereas neither resolved in RAG-1(-/-) mice. When C57BL/6 lymphocytes were adoptively transferred into RAG-1(-/-) mice, resolution of the infection and inflammation occurred. Mice without B cells were able to clear the infection, whereas mice without T cells could not clear it. In vitro stimulation of the draining lymph nodes of the infected mice by use of heat-killed S. pneumoniae led to the production of interferon (IFN)- gamma. Flow-cytometric analysis of lymphocytes obtained from sinus mucosa and draining lymph nodes showed an increase in the number of type 1 T helper cell-like cells over that in control mice. CONCLUSIONS RAG-1(-/-) mice with innate immunity but no lymphocytes contain--but cannot clear--a bacterial sinus infection. Lymphocytes transferred to RAG-1(-/-) mice clear the infection. The sinus mucosa and draining lymph nodes show an increase in T cells generating IFN- gamma. These data demonstrate that T cells are essential in clearing an acute S. pneumoniae bacterial sinus infection.

Allergic rhinitis augments the response to a bacterial sinus infection in mice: A review of an animal model.

Background Sinusitis is a poorly understood disease. Despite the significant morbidity and the enormous cost of treating sinusitis, little progress has been made at improving our understanding of its pathophysiology. One reason for restricted progress in understanding the disease is the lack of a satisfactory animal model that mimics sinusitis in man. Objective We review data establishing the development of sinusitis in mice after instillation of Streptococcus pneumoniae, the most common pathogen responsible for acute sinusitis in man. We also review data showing that allergic inflammation in mice worsens a subsequent bacterial sinusitis. We use this data to hypothesize how allergic inflammation worsens a bacterial sinus infection. Methods Different strains of mice were made allergic and/or infected. Results We show our ability to generate an allergic reaction in the nose after sensitization to ovalbumin. Our data further show that an ongoing allergic nasal reaction worsens acute sinusitis. Conclusion A mouse model has been created for a study of the interaction of allergic rhinitis and acute bacterial sinusitis.

Desloratadine partially inhibits the augmented bacterial responses in the sinuses of allergic and infected mice

Background Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown.