Recognition of one form of melanin by a lectin receptor is required fof immunity against Aspergillus

“Melanins” refer to a group of pigments containing indoles (and other intermediary products) derived from tyrosine oxidation. Melanin is widely distributed in the animal and plant kingdoms, and in vertebrates (animals having a spine) melanins are the major pigment present in surface structures (skin, hair follicles). Melanin is known to have many biological functions, and this article [attached] demonstrates one more function –– requirement for immunity against a specific (and common) form of fungus, Aspergillus fumigatus –– which can be lethal in patients who have a suppressed immune system (such as those who have undergone transplantation surgery). Melanins can provide protection against DNA-damaging ultraviolet radiation, are able to reinforce fungal cell-wall strength, and can improve microbial virulence.

Authors [attached article] identified a protein (MelLec) that can recog­nize a specific type of melanin produced by Aspergillus. Their data elucidate the immune-system response to a fungal infection. Human disease caused by Aspergillus is called aspergillosis. If one develops a lung infection after inhaling A. fumigatus spores, this can result in an infection that spreads elsewhere in the body [on the pediatrics ward, I recall a 4-year-old female patient “Rosie” from southern California with disseminated aspergillosis]. When Aspergillus fumigatus infects the lungs, host cells can trigger a cellular-degradation pathway called autophagy that helps destroy the fungus. However, melanin derived from the fungus can also inhibit autophagy.

Authors [see attached] screened members of the C-type lectin protein fam­ily (which had previously been identified as being involved in antifungal defense). Authors tested whether any C-type lectins from mice can bind fungal spores from A. fumigatus. One of the proteins they tested could do so, and they named it MelLec. They then tested strains of fungus containing mutations that block steps in the melanin-synthesis pathway, and found MelLec recognizes 1,8-dihydroxynaphthalene melanin, and MelLec did not recognize any other tested forms of melanin that are associated with fungal disease.

Resistance to Aspergillus infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. MelLec therefore recognizes an immunologically active component commonly found on the cell surfaces of fungi and has an essential role in protective antifungal immunity in both mice and humans. These findings might help in the discovery of new drug(s) to combat aspergillosis.

Nature 15 Mar 2018; 555: 382–386 [full article] & 319–320 [News-N-Views]

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