title: Teleost leukocyte immune-type receptors activate distinct phagocytic modes for target acquisition and engulfment.
abstract: Channel catfish (Ictalurus punctatus) IpLITRs belong to the Ig superfamily and regulate innate immune cell effector responses. This study tested the hypothesis that ITAM-dependent and ITAM-independent phagocytic pathways are engaged by different subtypes of the IpLITR family. When stably expressed in RBL-2H3 cells, the ITAM-containing fusion-construct IpLITR 2.6b/IpFcRγ-L stimulated phagocytic responses that were abrogated at suboptimal incubation temperatures and by pharmacological inhibitors of the classic signaling components of the mammalian FcR-dependent phagocytic pathway. Interestingly, the ITIM-containing receptor IpLITR 1.1b also induced phagocytosis through an actin-dependent mechanism, but this process was insensitive to the pharmacological inhibitors tested and remained functional at temperatures as low as 22°C. The IpLITR 1.1b also displayed a unique target-acquisition phenotype that consisted of complex, membranous protrusions, which captured targets in phagocytic cup-like structures but often failed to completely engulf targets. Taken together, these findings suggest that teleost immunoregulatory receptors that associate with ITAM-containing adaptors can engage conserved components of the phagocytic machinery to engulf extracellular targets akin to the classic FcR-mediated response in mammals. Alternatively, IpLITR 1.1b displays a stalled phagocytic phenotype that is likely dependent on the selective recruitment of the minimal molecular machinery required for target capture but results in incomplete target engulfment. Overall, this study demonstrates that IpLITRs can selectively engage distinct components of the phagocytic process and provides important new information regarding the target acquisition as well as internalization mechanisms involved in controlling phagocytic responses across vertebrates.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Dustin M E
authors.initials: DM
authors.lastname: Lillico
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Myron A
authors.initials: MA
authors.lastname: Zwozdesky
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Pemberton
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Julianna M
authors.initials: JM
authors.lastname: Deutscher
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lena O
authors.initials: LO
authors.lastname: Jones
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John P
authors.initials: JP
authors.lastname: Chang
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada stafford@ualberta.ca.
authors.forename: James L
authors.initials: JL
authors.lastname: Stafford
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology; D020816:Amino Acid Motifs; D000818:Animals; D029941:Fish Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D007059:Ictaluridae / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008863:Microspheres; D008969:Molecular Sequence Data; D010587:Phagocytosis; D010641:Phenotype; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013696:Temperature; D014162:Transfection
chemical_list: D000199:Actins; D029941:Fish Proteins; D047428:Protein Kinase Inhibitors; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C028495:phagocytosis receptor; D011494:Protein Kinases
keywords: comparative immunology; fish; immunoregulatory receptors; intracellular signaling; phagocytosis