Editors' ChoiceAsthma

Gammaherpesvirus is nothing to sneeze at

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Science Translational Medicine  25 Oct 2017:
Vol. 9, Issue 413, eaap8178
DOI: 10.1126/scitranslmed.aap8178


Gammaherpesvirus protects against allergic asthma by inducing the replacement of alveolar macrophages.

Challenging experiences can bring the opportunity for meaningful change. When confronted with new problems, seeking the help of outsiders can help fix what’s broken. That’s what Machiels and colleagues found in the lung: after gammaherpesvirus infection in mice, resident alveolar macrophages are partially replaced by newly recruited monocytes, which promote a less allergic environment.

Western countries have experienced a rise in allergic diseases such as hay fever and asthma. The hygiene hypothesis postulates that the reduction in childhood infectious diseases has led to this rise in allergy. To explore this idea, the investigators examined how intranasal infection with murid herpesvirus 4 (MuHV-4) altered the subsequent development of allergic asthma. MuHV-4 is in the gammaherpesvirus family, as is Epstein Barr Virus, which causes widespread infections in humans. The authors found that mice previously infected with MuHv-4 developed reduced histologic evidence of allergic disease after challenge with house dust mites (HDMs). MuHv-4 infection impaired the response of TH2 subset of helper T cells, whose over-activation can drive allergic responses such as hay fever, eczema, and asthma. The protective effect of MuHV-4 infection lasted for several months. Infection caused the death of alveolar macrophages (AMs), an embryonically derived, tissue-resident population in the lungs. The AMs were replaced by monocytes from the bone marrow, which remarkably developed a more regulatory phenotype, with a gene expression and cytokine production profile less reflective of allergic responses. The newly arrived monocyte-derived macrophages influenced their dendritic cell (DC) neighbors, which transport antigen to the lymph node and activate T cells. The monocyte-derived macrophages prevented DCs from triggering an HDM-specific TH2 response. These newly recruited macrophages were central to protection from allergy: if they were depleted, the MuHV-4 infected animals were no longer protected. Additionally, transfer of these retrained alveolar macrophages to an uninfected animal was sufficient to protect against HDM-induced airway allergy.

Although the protection against allergy was shown to last for several months, the jury is still out on longer-term durability, as well as the consequences on other types of pulmonary challenge. The results, however, raise the intriguing possibility that combining alveolar macrophage ablation and immunologic modulation might allow us to repair pulmonary disease states. Bringing in a little fresh blood might lead to a positive life change.

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