Dissecting the Mammalian Propensity for Cytokine Storms, Even in the Deep Blue Sea

Clinical data (on patients from elephant seals to people) make clear the extraordinary and contradictory powers of the mammalian immune system: a vital line of defense, yet a source of grave danger. For example, outcomes of infection by a given parasite strain can range from mildly symptomatic recovery through to death, and fatal cases are often associated with “cytokine storms” – i.e., violently-escalating host responses driven by cytokines, which are key signaling molecules of the immune system. Indeed, signaling feedback loops among different factions of cytokines are critical determinants of whether the infection is acute or chronic, and whether the host lives or dies. Theory predicts that baseline immune state – including contributions of host genetics and environment to white blood cell distribution at the time of parasite exposure – will determine whether a cytokine storm will ensue. Within this framework, we are seeking to explain the peculiar incidence of cytokine storms in northern elephant seals. Lungworms induce such potent cytokine storms in these seals that they die of disseminated coagulopathies that afflict no other host species. Northern elephant seals are exceptional in other ways, too. For example, they are among the deepest mammalian divers, and they were hunted nearly to extinction in the 1800s. By combining genomics and white blood cell transcriptomics with epidemiological and clinical data, we are beginning to reveal predictors of their propensity to mount cytokine storms. This work holds insights for conservation immunology, for evolutionary ecology, and for complex systems science.