Allergic Asthma Favors Brucella Growth in the Lungs of Infected Mice

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.

Eosinophils and Macrophages within the Th2-Induced Granuloma: Balancing Killing and Healing in a Tight Space

“…In addition, intestinal eosinophils have an increased half-life over blood or lung eosinophils (106). Specific eosinophil subsets are continually being identified (143), including a GR1 ϩ eosinophil population (144) (GR1 is typically a neutrophil marker). This makes eosinophil identification all the more difficult and highlights the importance of using tools such as the eosinophil reporter mouse (145) to assess eosinophil subsets and functions.…”

Exacerbation of Mycobacterium avium pulmonary infection by comorbid allergic asthma is associated with diminished mycobacterium-specific Th17 responses

“…Similar to our results, infection with intracellular pathogens of the Brucella family is reportedly exacerbated by exposure to allergens via IL-4/STAT6 signaling. However, infection with Streptococcus pneumoniae , an extracellular pathogen, is alleviated by allergen exposure, whereas Mtb infection is not altered under conditions of comorbidity [ 26 ]. Monin et al studied the effect of Aspergillus fumigatus , which commonly coinfects NTM, on Mycobacterium abscessus infection.…”

“…The coexistence of NTM-PI and allergic asthma is likely to accelerate the progression of both diseases; thus, a general understanding of comorbid conditions regarding pathology and immunology is clinically important. Although many studies have revealed mycobacterial infection-related conditions comorbid with allergic asthma from various perspectives of allergic asthma [ 23 , 24 ], only a few studies have investigated immunological progression [ 25 , 26 ]. Moreover, to our knowledge, whether these chronic diseases influence one another has not been investigated in previous experimental studies or clinical settings.…”

Route of Infection Strongly Impacts the Host-Pathogen Relationship

“…infected wild-type mice. Brucella -infected neutrophils have been described in pathological conditions (69). To our knowledge, this is the first description of Brucella -infected fibroblasts in vivo in wild-type mice.…”