Preexisting helminth infection induces inhibition of innate pulmonary anti-tuberculosis defense by engaging the IL-4 receptor pathway.

Abstract

Tuberculosis and helminthic infections coexist in many parts of the world, yet the impact of helminth-elicited Th2 responses on the ability of the host to control Mycobacterium tuberculosis (Mtb) infection has not been fully explored. We show that mice infected with the intestinal helminth Nippostrongylus brasiliensis (Nb) exhibit a transitory impairment of resistance to airborne Mtb infection. Furthermore, a second dose of Nb infection substantially increases the bacterial burden in the lungs of co-infected mice. Interestingly, the Th2 response in the co-infected animals did not impair the onset and development of the protective Mtb-specific Th1 cellular immune responses. However, the helminth-induced Th2 environment resulted in the accumulation of alternatively activated macrophages (AAMs) in the lung. Co-infected mice lacking interleukin (IL) 4Rα exhibited improved ability to control Mtb infection, which was accompanied by significantly reduced accumulation of AAMs. Moreover, IL-4Rα(-/-) mice adoptively transferred with wild-type macrophages had a significantly higher Mtb load in their lungs compared with those that received IL-4Rα(-/-) macrophages, suggesting a direct contribution for the IL-4R pathway to the heightened susceptibility of co-infected animals. The Th2 response can thus enhance the intracellular persistence of Mtb, in part by mediating the alternative activation of macrophages via the IL-4Rα signaling pathway.

• Authors: Julius A Potian, Wasiulla Rafi, Kamlesh Bhatt, Amanda McBride, William C Gause, Padmini Salgame
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 208 Issue 9 Pg. 1863-74 (Aug 29 2011) ISSN: 1540-9538 [Electronic] United States
• PMID: 21825018 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2011 Potian et al.

Chemical References

• Il4ra protein, mouse
• Receptors, Cell Surface

Topics

• Animals
• Immunity, Cellular (genetics)
• Immunity, Innate
• Lung (immunology)
• Macrophages (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Mycobacterium tuberculosis (immunology)
• Nippostrongylus (immunology)
• Receptors, Cell Surface (genetics, immunology)
• Signal Transduction (genetics, immunology)
• Strongylida Infections (genetics, immunology)
• Th1 Cells (immunology)
• Th2 Cells (immunology)
• Tuberculosis, Pulmonary (genetics, immunology)