Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: A mouse model

Abstract

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)-γ. 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-γ. These data demonstrate that T cells are essential in clearing an acute S. pneumoniae bacterial sinus infection. © 2005 by the Infectious Diseases Society of America. All rights reserved.