Novel Role for Animal Innate Immune Molecules: Enterotoxic Activity of a Snail Egg MACPF-Toxin

GIGLIO, M.L.; ITUARTE, S; IBAÑEZ, ANDRÉS E.; DREON, M.S.; PRIETO, ED; FERNANDEZ, PE; HERAS, H

PERFORINS AND CHOLESTEROL-DEPENDENT CYTOLYSINS IN IMMUNITY AND PATHOGENESIS

Frontiers

Lugar: Lausanne; Año: 2022; p. 20 - 33

In humans and other mammals, the pore-forming proteins C9 and the perforins are importantinnate immune effectors. C9 forms the membrane attack complex (MAC) in an assemblage with thecomplement proteins C5b, C6, C7, and C8 that attacks the envelopes of gram-negative bacteria.Perforin is deployed by degranulating killer lymphocytes to destroy virally infected or cancerouscells. The product of macrophage expressed gene 1 (Mpeg1), named perforin-2 by the late EckhardR. Podack (1943–2015), appears to play a central role in the destruction of phagocytosed bacteria.All three pore-forming proteins contain a membrane attack complex-perforin (MACPF) domain.However, the MACPF domain is not exclusive to mammals. Rather, proteins with MACPF domainsare found in a diverse array of taxa including plants, fungi, invertebrates, and a variety of protozoanssuch as the malaria parasite Plasmodium falciparum, or Toxoplasma gondii, the causative agent oftoxoplasmosis. MACPF domains have also been identified in some prokaryotes includingpathogenic species of Chlamydia. Pore-forming proteins within the MACPF family share acanonical fold with the cholesterol-dependent cytolysins (CDCs) (1). CDCs are pore-formingproteins that contribute to the virulence of several gram-positive pathogens such as Clostridiumperfringens, Listeria monocytogenes, and group A streptococci. Thus, evolution has produced poreforming proteins with opposing roles in host defense and pathogenesis that have shared structuralfeatures. As previewed below, this article collection highlights the immunological and pathologicalroles of MACPF/CDC pore-forming proteins.