Abstract
Allergic asthma is a chronic Th2 inflammatory disease of the lower airways affecting a growing number of people worldwide. The impact of infections and microbiota composition on allergic asthma has been investigated frequently. Until now, however, there have been few attempts to investigate the impact of asthma on the control of infectious microorganisms and the underlying mechanisms. In this work, we characterize the consequences of allergic asthma on intranasal (i.n.) infection by Brucella bacteria in mice. We observed that i.n. sensitization with extracts of the house dust mite Dermatophagoides farinae or the mold Alternaria alternata (Alt) significantly increased the number of Brucella melitensis, Brucella suis, and Brucella abortus in the lungs of infected mice. Microscopic analysis showed dense aggregates of infected cells composed mainly of alveolar macrophages (CD11c+ F4/80+ MHCII+) surrounded by neutrophils (Ly-6G+). Asthma-induced Brucella susceptibility appears to be dependent on CD4+ T cells, the IL-4/STAT6 signaling pathway and IL-10, and is maintained in IL-12- and IFN-γR-deficient mice. The effects of the Alt sensitization protocol were also tested on Streptococcus pneumoniae and Mycobacterium tuberculosis pulmonary infections. Surprisingly, we observed that Alt sensitization strongly increases the survival of S. pneumoniae infected mice by a T cell and STAT6 independent signaling pathway. In contrast, the course of M. tuberculosis infection is not affected in the lungs of sensitized mice. Our work demonstrates that the impact of the same allergic sensitization protocol can be neutral, negative, or positive with regard to the resistance of mice to bacterial infection, depending on the bacterial species.
Highlights
One striking feature of infectious diseases is the marked interindividual variation in susceptibility/ resistance
As chronic IL-4-dominated Th2 response induced by helminthes is well known to negatively affect the Th1 response [35,36,37,38,39,40,41], we compared the ability of groups of mice subjected to i.n. sensitization with phosphate-buffered saline (PBS), house dust mite Dermatophagoides farinae (HDM), or Alt for 17 days to control i.n
We chose a dose of Brucella infection similar to that used in our previous characterization of the B. melitensis intranasal infection model [23]: 2 × 104 CFU, as described in the Section “Materials and Methods.”
Summary
One striking feature of infectious diseases is the marked interindividual variation in susceptibility/ resistance. Allergic asthma is one of the most common lung diseases It affects an estimated 300 million people worldwide [2] and its prevalence continues to increase in many parts of the world [3]. It is characterized by recurring symptoms of reversible airflow obstruction, bronchial hyperresponsiveness and lower airway inflammation. Despite the significant proportion of people worldwide affected by asthma and though some epidemiological studies [6,7,8] report increasingly severe bacterial and viral infections in asthma patients, little effort has been made to investigate the impact of asthma on the control of infectious microorganisms and identify the underlying mechanisms
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