Finding a mate can be a challenge, especially in the ocean where the chance of bumping into a potential partner is scarce. So, some species of anglerfish have evolved to permanently or semi-permanently join with their mates. Dwarfed males use their jaws to latch onto females that are 60 times their size, fusing their tissues and blood circulation to those of their mate. This clingy relationship, known as sexual parasitism, means that the males are sustained by the females. In return, males only need to supply their sperm. From the perspective of the immune system, this type of parasitism should be prevented by robust immune responses. How is it that the female anglerfish’s immune system does not reject the parasitic male, as it would any other parasite?

Immune evolution: protect the self, eliminate the non-self

Being able to fuse tissues with another organism goes against the rules of the immune system. Over time, the immune system has evolved to protect the body against foreign entities like bacteria, viruses, and parasites, as these generally pose a threat to the health of the organism. Evolutionarily speaking, foreign or “non-self” tissue should alarm the immune system the same way that a bacterial cell would, making immune cells go on the offensive to eliminate the potential threat. An example of this attack of “non-self” tissues occurs during organ transplant rejection, with recipients requiring drugs to dampen the immune system and prevent attack of the new organ. 

Sexual parasitism in anglerfish defies these evolutionary rules. To the surprise of immunologists, anglerfish have actually evolved to bypass tissue rejection and evade typically protective immune responses. A team of scientists at the Max Planck Institute of Immunobiology and Epigenetics and the University of Washington studied how the immune system of anglerfish permit the fusing of organisms. 

Anglerfish: the rebels of the sea 

The researchers came up with 3 hypotheses that might explain this phenomenon: 1) anglerfish only  fuse with mates that are genetically similar to themselves so that the tissue of a mate doesn’t look foreign to the immune system, 2) anglerfish all are so genetically identical that rejection does not occur, or 3) anglerfish have a defective immune system, allowing for a tempered immune response to the fused tissues.

Using the genetic sequence of multiple species of anglerfish, the researchers compared temporarily attaching, permanently attaching with one male, permanently attaching with multiple males, and non-parasitizing species. The researchers compared the MHC (major histocompatibility complex) genes across the different parasitizing and non-parasitizing groups. MHC molecules are a group of proteins that decorate the surface of nearly every cell in the body and function in communicating with immune cells. Just like a mannequin on a window display can be dressed with different clothes to give a sneak peak of what’s inside a store, the MHC is “dressed” with protein fragments that communicate with the immune system about what is present inside the cell. When these protein fragments are derived from foreign proteins, as would happen if the cell had been infected with bacteria or viruses, immune cells known as T cells sense danger and galvanize an attack on the source of the MHC-bound foreign protein. 

After comparing MHC genes between species, the researchers found that while non-parasitizing and temporarily attaching species had a high number of MHC genes, some MHC genes were altered in the permanently attaching species. This observation supports hypothesis #3, since the disruption of communication between immune cells leads to a defective immune response, thereby preventing tissue rejection (Figure 1). 

The researchers also found that additional immune dysfunction in the anglerfish occurs by genetic changes in other immune related genes. The permanently attaching species exhibited a loss in T cell genes, as well as a loss in a gene which is involved in the production of antibodies, known as the AICDA gene (Figure 2). T cells have receptors on their surfaces that interact with MHC, so the loss in T cell genes results in lowered immune detection of foreign proteins. Antibodies are secreted by other immune cells, called B cells, and bind to foreign particles to mark them for immune attack. A lack in T cells and antibodies means that the immune responses of these anglerfish is compromised. To the benefit of anglerfish reproduction and sexual parasitism, this malfunctioning adaptive immune system permits the attachment of tissues from other organisms for extended periods of time. 

Immune dysfunction: a dangerous balancing act 

While this study answered important questions regarding anglerfish immunity, a compromised immune system that dodges tissue rejection would predictably be more susceptible to other foreign invaders. The presence of microbes in the deep-sea environment means that anglerfish face threats from their surroundings and need efficient immune responses to maintain good health. So how do anglerfish maintain integrity of their tissues and protect themselves against outside threats? A potential explanation is that these anglerfish may have evolved to have a different immune system than other vertebrates, but more work will be needed to flesh out this hypothesis Determining how organisms break the rules of the immune system but still survive can contribute to a broader understanding of immunology, and potentially help us develop better ways to treat human disease.

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Cover image courtesy of Masaki Miya et al., CC BY 2.0, via Wikimedia Commons