A Lucilia cuprina excretory-secretory protein inhibits the early phase of lymphocyte activation and subsequent proliferation.
The development of a protective immune response in sheep towards the presence of the larval stage of Lucilia cuprina has not been reported in the field. Upon investigation of the effects of larval excretory/secretory material on ovine T lymphocyte proliferation, we isolated a 56 kDa protein capable of inhibiting lymphocyte proliferation by at least 70%, compared with that in the presence of mitogen alone. This protein inhibited proliferation induced through cross-linking of the T-cell receptor as well as proliferation induced pharmacologically through the stimulation of the protein kinase C (PKC) pathway. The protein, named blowfly larval immunosuppressive protein (BLIP), was shown to bind directly to lymphocytes. Further investigation revealed that the BLIP prevented a proportion of lymphocytes from entering the first division following stimulation, by affecting the early events in lymphocyte activation. Subsequently, the BLIP reduced CD25 expression on T lymphocytes, reduced IL-2 mRNA expression, in addition to IFN-gamma, IL-4, IL-10 and IL-13 mRNA expression. Conversely, TNF-alpha and TGF-beta gene expression was up-regulated in response to the BLIP. These effects suggest suboptimal activation of T lymphocytes in the presence of the BLIP, and we propose that the BLIP presents an effective immune evasion tactic for the larvae of L. cuprina.
Elkington
R A
RA
Queensland Agricultural Biotechnology Centre, University of Queensland, Brisbane, Qld, Australia. rebecca.elkington@dpi.qld.gov.au
Humphries
M
M
Commins
M
M
Maugeri
N
N
Tierney
T
T
Mahony
T J
TJ
D056704:Adaptive Immunity; D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004175:Diptera / Q000276:immunology*; D005786:Gene Expression Regulation; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D009198:Myiasis / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D011485:Protein Binding; D016415:Sequence Alignment; D012756:Sheep / Q000276:immunology / Q000469:parasitology*; D012757:Sheep Diseases / Q000276:immunology* / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D019476:Insect Proteins; D053645:Interleukin-2 Receptor alpha Subunit