Immune functions switched for reproductive success

The deep sea monkfish employs an incredible reproductive strategy. Small dwarf males permanently attach to relatively gigantic females, fuse their tissues together, and then establish a common blood circulation. In this way, the man becomes completely dependent on the woman for the supply of nutrients, such as a developing fetus in her mother’s womb or a donor organ in a transplant patient. In monkfish, this unusual phenomenon is known as sexual parasitism and contributes to the reproductive success of these animals that live in the vast space of the deep sea, where females and males are rarely found.

The permanent attachment of males to females represents a form of anatomical union, which is otherwise unknown in nature, except for the rare occurrence in genetically identical twins. The immune system represents an extraordinary obstacle. It attacks foreign tissue as it would destroy pathogen-infected cells. Just look at the difficulties surrounding human organ transplantation, requiring a careful cross-combination of donor and recipient tissue types, along with immunosuppressive medications, to ensure long-term survival of organ grafting. But how is it possible that fish are so readily accepted when tissue rejection might be expected?

The phenomenon of sexual parasitism has posed a conundrum that has been around for 100 years, ever since the first united couple was discovered by an Icelandic fishery biologist in 1920. Scientists from Germany and the United States have now solved this centuries-old conundrum and report their findings in the scientific journal Science.

Key immune system functions removed

A few years ago, Thomas Boehm, a physician and immunologist working at the Max Planck Institute for Immunobiology and Epigenetics in Freiburg, Germany, and Theodore W. Pietsch, an internationally recognized ichthyologist and angler fishery expert working at the University of Washington in Seattle, he set out to study the genomes of different monkfish species. They started by looking at the structure of the major histocompatibility antigens (MHC). These molecules are found on the surface of body cells and send an alarm signal to the immune system when the cells are infected by a virus or bacteria. To ensure that all pathogens are recognized efficiently, MHC molecules are extremely variable, so much so that it is difficult to find identical or nearly identical forms in either of the two individuals of a species. This feature is the root of the tissue mismatch problem that affects organ transplantation and human bone marrow.

Interestingly, the researchers found that angler fish that use permanent fixation are largely impoverished in the genes that encode these MHC molecules, as if they had eliminated immune recognition in favor of tissue fusion. “In addition to this unusual constellation of MHC genes, we found that the function of killer T cells, which normally actively kill infected cells or attack foreign tissues during the organ rejection process, is also severely attenuated if not completely lost. These findings hinted that the monkfish fish immune system is highly unusual among the tens of thousands of vertebrate species, “says Jeremy Swann of the MPI for Immunobiology and Epigenetics and first author of the study.

Survival without acquired immune facilities

After these unexpected discoveries, scientists suspected that the reorganization of the monkfish’s immune system might be even more extensive than expected. And, in fact, further research indicated that the antibodies, which are the second most powerful weapon in the immune defense arsenal, are also lacking in some monkfish species. “For humans, the combined loss of important immune facilities observed in monkfish would result in fatal immunodeficiency,” says Thomas Boehm, MPI Director of Immunobiology and Epigenetics and chief scientist for the project.

However, angler fish can obviously survive without essential adaptive immune functions. Thus, the researchers concluded that animals use much better innate facilities to fend off infections, an unexpected solution to a problem faced by all living things. In fact, until now, it was thought that an association of acquired and innate immunity, once formed in evolution, cannot be unraveled without serious consequences.

The immune system affects reproductive strategy.

Thus, the study shows that, despite several hundred million years of coevolutionary association of innate and adaptive functions, vertebrates can survive without adaptive immune facilities previously considered irreplaceable. We assume that the yet unknown evolutionary forces first drive changes in the immune system, which are then exploited for the evolution of sexual parasitism, “says Thomas Boehm.

Interestingly, scientists believe that among their collection of fish, they have even caught one species on the way to developing sexual parasitism. “We find it remarkable that the unusual mode of reproduction was invented several times independently in this group of fish,” says Ted Pietsch of the University of Washington.

Although the details of improved innate immune facilities in monkfish have not yet been discovered, the results of this study point to potential strategies that improve innate immune facilities in human patients suffering the consequences of innate or acquired impairment of immune facilities. . Thus, the scientific journey that began with a dark observation aboard a fishing boat in the middle of the Atlantic unexpectedly opens up new avenues for treating immune disorders in humans.