Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T-cells

Abstract

An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD).Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed.Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment.Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.

Pneumococcal Components Induce Regulatory T Cells That Attenuate the Development of Allergic Airways Disease by Deviating and Suppressing the Immune Response to Allergen

“…We have previously shown that live or killed Streptococcus pneumonia (i.e., the pneumococcus) as well as pneumococcal vaccines suppress the hallmark features of AAD in mouse models of asthma. Thus, antigenic components of S. pneumoniae have the potential to be used as immunoregulatory therapies for asthma (8)(9)(10). We have also demonstrated that suppression of AAD by S. pneumoniae is mediated by the induction of Tregs.…”

“…Cells were permeabilized and stained intracellularly for Foxp3, according to the manufacturer's protocol (eBioscience) (8). For detection of IL-6 and IL-17, cells were stimulated with LPS (100 ng/ml) for 20 h or PMA (0.1 mg/ml) and ionomycin (1 mg/ml) for 6 h, respectively.…”

“…Single-cell suspensions were prepared from MLNs by pushing through 70-mm sieves and from lungs and spleens using a gentle MACs homogenizer (Miltenyi Biotec, Auburn, CA), according to the manufacturer's protocol (8).…”

The Contrasting Roles of T Regulatory Cells in Bacterial Lung Diseases

“…Suggested methods for how to stimulate the development of T reg cell responses vary. Interestingly, one possible approach involves treatment of patients with bacteria or bacterial products (Fonseca & Kline, 2009;Trujillo & Erb, 2003), and indeed, there are cases in which this type of therapy has been experimentally validated (Crother et al, 2011;Preston et al, 2011;Thorburn et al, 2010). This promising approach may have a broader utility since, as discussed in this article, different kinds of bacteria appear to be able to elicit different types of T reg cell responses.…”

“…Despite its role as the quintessential pneumococcal pathogen, very little work has been performed in the area of S. pneumoniae and T reg cells. In studies that examined the role of Streptococcus in asthma and airway hyperreactivity, it was shown that both intact S. pneumoniae and pneumococcal proteins can induce the development of T reg cells (Preston et al, 2011;Thorburn et al, 2010). The role of T reg cells in pneumococcal disease is unclear, but recent studies have begun examining the role of T reg cells in the generation of humoral immune responses against S. pneumoniae.…”