Acinetobacter baumannii Infection Inhibits Airway Eosinophilia and Lung Pathology in a Mouse Model of Allergic Asthma

Abstract

Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen.

Immunization against Multidrug-Resistant Acinetobacter baumannii Effectively Protects Mice in both Pneumonia and Sepsis Models

“…It has been reported that the intranasal administration of A. baumannii induces Th1 type responses and thus suppresses subsequent OVA-stimulated Th2 type airway allergic inflammation responses [36]. In the current study, IL-33 and IL-13 were found to be significantly elevated in the pneumonia model.…”

Toxoplasma gondii Infection Induces Suppression in a Mouse Model of Allergic Airway Inflammation

“…This conclusion initially came from epidemiological data that allowed establishing a link between decreased childhood infections and increased allergy in western countries [4]–[6]. Later, many clinical and experimental studies with several microbes or their products supported the hypothesis [7]–[14].…”

Salmonella enterica Serovar Typhimurium Infection-Induced CD11b+Gr1+Cells Ameliorate Allergic Airway Inflammation

“…Colonization of the intestinal tract by commensal bacteria like Enterobacteriaceae, Clostridium, and Bifidobacterium has been shown to induce Treg cells, resulting in the prevention of inflammatory bowel disease and maintenance of mucosal tolerance (37,38). In contrast to certain commensal bacteria and helminths and in accordance with other infection models like Acinetobacter lwoffii F78 and Acinetobacter baumannii, S. Typhimurium infection exhibited no demonstrable change in the frequencies and numbers of Foxp3 ϩ Treg cells (12,13). Subsequently, we detected a considerable increase in a population of cells expressing CD11b and Gr1 in the spleens and lungs of mice infected with S. Typhimurium.…”

“…Induction and expansion of Treg cells during various helminth and bacterial infections have led to the inhibition of allergic airway inflammation in mouse models (7)(8)(9)(10)(11). In contrast, certain infection models have also confirmed suppression of allergies in a Treg cell-independent manner, for which the mechanisms are yet undefined (12,13).…”