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The protective effects of mycobacterial infections on lung allergy are well documented. However, the inverse relationship between tuberculosis and type 2 immunity is still elusive. Although type 1 immunity is essential to protection against Mycobacterium tuberculosis it might be also detrimental to the host due to the induction of extensive tissue damage. Here, we determined whether lung type 2 immunity induced by allergen sensitization and challenge could affect the outcome of M. tuberculosis infection. We used two different protocols in which sensitization and allergen challenge were performed before or after M. tuberculosis infection. We found an increased resistance to M. tuberculosis only when allergen exposure was given after, but not before infection. Infected mice exposed to allergen exhibited lower bacterial load and cellular infiltrates in the lungs. Enhanced resistance to infection after allergen challenge was associated with increased gene expression of alternatively activated macrophages (M2 macrophages) and IL-33 levels. Accordingly, either adoptive transfer of M2 macrophages or systemic IL-33 treatment was effective in attenuating M. tuberculosis infection. Notably, the enhanced resistance induced by allergen exposure was dependent on IL-33 receptor ST2. Our work indicates that IL-33 might be an alternative therapeutic treatment for severe tuberculosis., Competing Interests: The authors declare no competing financial interests.

Tuberculosis (TB) remains a threat for public health, killing around 3 million people a year. Despite the fact that most cases can be cured with antibiotics, the treatment is long and patients relapse if chemotherapy is not continued for at least 6 months. Thus, a better characterization of the working principles of the immune system in TB and identification of new immunotherapeutic products for the development of shorter regimens of treatment are essential to achieve an effective management of this disease. In the present work, we demonstrate that immunotherapy with a plasmid DNA encoding the Mycobacterium leprae 65 kDa heat-shock protein (hsp65) in order to boost the efficiency of the immune system, is a valuable adjunct to antibacterial chemotherapy to shorten the duration of treatment, improve the treatment of latent TB infection and be effective against multidrug-resistant bacilli (MDR-TB). We also showed that the use of DNA-hsp65 alone or in combination with other drugs influence the pathway of the immune response or other types of inflammatory responses and should augment our ability to alter the course of immune response/inflammation as needed, evidencing an important target for immunization or drug intervention.