Mice that previously experienced a roundworm infection react less severely to a dangerous influenza virus. Thanks to this more tolerant immune response, they become much less ill, researchers report in Nature. ‘This could be of great value during future pandemics.’
One person may be bedridden with the flu for a week, while another experiences hardly any symptoms from the same virus. How is that possible? Growing evidence suggests that people become seriously ill primarily when their own immune system goes into overdrive. This causes damage to the lungs and leads to symptoms. Whether someone clears the virus quickly or slowly appears to be less important.
Early in the COVID-19 pandemic, researchers at NYU Grossman School of Medicine in New York and Radboud university medical center in Nijmegen noted that regions where parasitic worm infections are common were seeing milder disease. That raised the question of whether a previous worm infection could change how the body responds to a respiratory virus.
Immune memory
It turns out that this is possible. The researchers, led by Kamal Khanna from New York, divided mice into two groups. One group was infected with a parasitic roundworm, while the other was not. Several weeks later, all mice were exposed to a dangerous influenza virus, H1N1. All mice that had previously been infected with roundworms survived the flu, whereas the mice without roundworm infections did not. The viral load was the same in all mice, meaning that the roundworm-infected mice were not clearing the virus any faster.
The researchers show that this protection works through a specialized type of macrophage, that the team had previously identified, a kind of immune cell that sits around the large airways and nerves of the lungs. ‘These cells store a previous encounter with a worm in a form of immune memory and subsequently promote a tolerant immune response during a later infection, in which the immune system reacts far less aggressively’, says PhD candidate Yavor Yordanov of Radboudumc. ‘As a result, less harmful inflammation develops, lung tissue recovers more quickly, and breathing remains better preserved.’
A different type of therapy
That these macrophages were indeed responsible for the tolerant response to influenza infection was demonstrated through several follow-up experiments. For example, the protective effect disappeared when the researchers removed these cells. Conversely, they were able to restore protection by transferring the cells to other animals. They also achieved the same protective effect using two purified signaling molecules, without using the parasitic worm itself. In addition, they identified similar macrophages isolated from human lungs.
These findings point to a different type of therapy: a treatment that does not target the virus itself, but rather the lung’s ability to tolerate infection. ‘Because such an approach does not depend on knowing exactly which virus is circulating, it could be of great value during future pandemics’, says Musa Mhlanga, professor at the Radboudumc. ‘Moreover, this strategy could be especially beneficial for people with underlying health conditions, as they are the most vulnerable to severe lung damage caused by infections.’
About the publication
This research was published in Nature: Type 2 immune history trains lung macrophages for viral disease tolerance. Payal Damani-Yokota, Yavor Yordanov, Eduardo D. Bernier, Chaitra Sreenivasaiah, Alireza Khodadadi-Jamayran, Matthias C. Kugler, Stephen T. Yeung, Stacey Bartlett, Valeria Mezzano, Eric Bartnicki, Mingjun Liu, Fei Chen, William C. Gause, Aristotelis Tsirigos, Iannis Aifantis, Mila B. Ortigoza, Bettina Nadorp, Musa M. Mhlanga, and Kamal M. Khanna. DOI: 10.1038/s41586-026-11060-y.
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Annemarie Eek
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