Recruitment and in situ Renewal Regulate Rapid Accumulation of CD11c+ Cells in the Lung following Intranasal Superantigen Challenge

Abstract

Background: Staphylococcusaureus, a primary source of bacterial superantigen, is known to colonize the human respiratory tract and has been implicated in airway inflammation. The potential pathological effect of staphylococcal enterotoxins on the respiratory tract necessitates a detailed understanding of how they regulate innate immune cells, particularly CD11c-expressing dendritic cells (DCs). Methods: C57BL/6 mice were challenged intranasally with staphylococcal enterotoxin A (SEA) and at indicated time points lung tissue was perfused, digested and analyzed for CD11c+ expressing cells. Results: The pulmonary CD11c+ cells can be divided into two major populations based on their MHC II expression. One day following intranasal SEA challenge, there was rapid accumulation of CD11c+ cells expressing medium to high levels of MHC II. The peak accumulation of CD11c+ MHC II– population was observed 2 days after SEA challenge; however, careful examination of this cell population revealed that they were heterogeneous, being comprised of cells bearing CD3, CD19, NK1.1 and F4/80 along with varying levels of CD11c. Nevertheless, there was a 2-fold increase of CD11c+ MHC II– (CD3– CD19– NK1.1– F4/80–) cells in the lungs. Conclusion: The mechanism of increase in the CD11c+ MHC II– immune progenitor population was mainly due to cellular division rather than migration from blood to lung. In contrast, the early and rapid accumulation of CD11c+ MHC II^hi cells, conventionally known as DCs, in the lung on day 1 was mostly due to migration from blood. Thus this study examines the pulmonary innate immune response to a powerful immune stimulus.

Inhalation of Staphylococcus aureus Enterotoxin A Induces IFN-γ and CD8 T Cell-Dependent Airway and Interstitial Lung Pathology in Mice

“…Moreover, there was also an increase of macrophages that was maintained through day 5. These data are consistent with a growing theme showing that SEA-induced T cell responses stimulate innate cells such as lung CD11c + cells, as we have recently observed (27). Taken together, future studies should provide a clearer picture on the precise role that each innate cell population contributes to disease.…”

“…Consistent with this idea are data showing that CD11c + cells rapidly accumulate in the lung after i.n. SEA treatment (27). It is also possible that SEA leaks into the bloodstream, although other studies have shown that SAg is rapidly absorbed by the immune system (29).…”

Exacerbation of cigarette smoke-induced pulmonary inflammation by Staphylococcus aureus Enterotoxin B in mice

“…In line with previously reported findings, in our model sole endonasal SEB application caused an increase in total BAL cell number, lymphocytes and neutrophils [16]. Moreover, we could demonstrate raised numbers of macrophages and dendritic cells, a finding previously reported after S. aureus enterotoxin A exposure [28,29]. In the latter studies however, the authors could not demonstrate increased eosinophils, which was the case in our model.…”

Superantigen-related TH2 CD4+ T cells in nonasthmatic chronic rhinosinusitis with nasal polyps

“…9 Abbreviations used CRS: Chronic rhinosinusitis CRSsNP: Chronic rhinosinusitis without nasal polyps CRSwNP: Chronic rhinosinusitis with nasal polyps CRTH2: Staphylococcal superantigens induce nasal polyposis by affecting a variety of cell types, including epithelial cells, lymphocytes, eosinophils, basophils, mast cells, and dendritic cells. [10][11][12][13][14][15][16] The net effect of superantigens in NPs is the production of T H 2 cytokines, regulatory T-cell inhibition, and accentuated eosinophil and mast cell activity, resulting in tissue damage and remodeling. 14,[16][17][18] Skewed distribution of T-cell receptor Vb chain (TCRVb) has also been reported in NPs as evidence of the pathogenicity of staphylococcal superantigens.…”