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

Abstract

Staphylococcus aureus, a primary source of bacterial superantigen (SAg), is known to colonize the human respiratory tract and has been implicated in airway inflammation. Studies have documented a role for SAgs in respiratory disorders, such as nasal polyps, chronic obstructive pulmonary disease, chronic rhinosinusitis, and asthma. However, cellular and molecular mediators involved in SAg-mediated pulmonary disease have not been clearly identified. In this study, we investigated the effect of intranasal staphylococcal enterotoxin A (SEA) exposure on murine lung. The pathological features in the lung resulting from SEA exposure had characteristics of both obstructive and restrictive pulmonary disorders. There was also an increase in bronchoalveolar lavage protein concentration and cellularity following SEA challenge. Massive CD8+Vβ3+ T cell accumulation observed in the lung was dependent on CD4 T cell help, both for recruitment and for IFN-γ synthesis. The primary source of IFN-γ synthesis was CD8 T cells, and depletion of these cells abrogated disease. IFN-γ deficiency also prevented SEA-mediated disease, and this was by enhancing early recruitment of neutrophils as detected in the bronchoalveolar lavage. Thus, IFN-γ appeared to selectively aid the recruitment of T cells to the lungs while preventing the neutrophil accumulation. Therefore, our results show that IFN-γ-producing CD8 T cells mediated pulmonary alveolitis and inflammation, which were dependent upon CD4 T cells for their recruitment to the lung.

Airway exposure to staphylococcal enterotoxin A potentiates allergen-induced bone marrow eosinophilia and trafficking to peripheral blood and airways

“…Interestingly, SEA alone (with no OVA challenge) significantly increased the eosinophil influx into the lung section, as observed at 4 to 48 h preexposure. This is consistent with previous studies showing the presence of pulmonary inflammatory infiltrates in animals exposed to SEA alone (17,29,30). It is intriguing, however, that SEA exposure alone promotes eosinophil infiltration into the lung with no accompanying changes in BM and circulating blood.…”

“…The eosinophil progenitors are currently defined as CD34 ϩ cells that coexpress IL-5 receptor alpha (IL-5R␣) on their surface (5,19,35,40). IL-5 itself upregulates its receptor (IL-5R␣) on CD34 ϩ progenitor cells acting in an autocrine manner (13,21,30). Allergic stimulation elevates the serum levels of IL-5 that further enhances the expression of IL-5 receptor (IL-5R1), expanding to 10-to 20-fold (or even greater) the BM eosinophil progenitor, thus promoting their differentiation into mature cells for release into the peripheral blood (41).…”

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

“…Our laboratory showed that intranasal (i.n.) SEA results in acute lung injury that depends on the activation of CD8 T cells and IFNγ, and importantly, this lung injury model also presents systemic effects (28). We tested if systemic pretreatment with poly(I:C) could mitigate the local and systemic responses to i.n.…”

Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice

“…An alternative model proposed in this study is intranasal inhalation of the organic dust. Intranasal administration of other agents, including, but not limited to, ultrafine particles, biomass particles, bacterial components, microbial superantigens, and allergens, are becoming increasingly utilized to investigate mechanisms of exaggerated airway inflammation in vivo (10,15,22,24,26).…”