The innate immune and systemic response in honey bees to a bacterial pathogen, Paenibacillus larvae.
BACKGROUND
There is a major paradox in our understanding of honey bee immunity: the high population density in a bee colony implies a high rate of disease transmission among individuals, yet bees are predicted to express only two-thirds as many immunity genes as solitary insects, e.g., mosquito or fruit fly. This suggests that the immune response in bees is subdued in favor of social immunity, yet some specific immune factors are up-regulated in response to infection. To explore the response to infection more broadly, we employ mass spectrometry-based proteomics in a quantitative analysis of honey bee larvae infected with the bacterium Paenibacillus larvae. Newly-eclosed bee larvae, in the second stage of their life cycle, are susceptible to this infection, but become progressively more resistant with age. We used this host-pathogen system to probe not only the role of the immune system in responding to a highly evolved infection, but also what other mechanisms might be employed in response to infection.


RESULTS
Using quantitative proteomics, we compared the hemolymph (insect blood) of five-day old healthy and infected honey bee larvae and found a strong up-regulation of some metabolic enzymes and chaperones, while royal jelly (food) and energy storage proteins were down-regulated. We also observed increased levels of the immune factors prophenoloxidase (proPO), lysozyme and the antimicrobial peptide hymenoptaecin. Furthermore, mass spectrometry evidence suggests that healthy larvae have significant levels of catalytically inactive proPO in the hemolymph that is proteolytically activated upon infection. Phenoloxidase (PO) enzyme activity was undetectable in one or two-day-old larvae and increased dramatically thereafter, paralleling very closely the age-related ability of larvae to resist infection.


CONCLUSIONS
We propose a model for the host response to infection where energy stores and metabolic enzymes are regulated in concert with direct defensive measures, such as the massive enhancement of PO activity.
Chan
Queenie W T
QW
Centre for High-Throughput Biology and Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. queeniecwt@shaw.ca
Melathopoulos
Andony P
AP
Pernal
Stephen F
SF
Foster
Leonard J
LJ
D000818:Animals; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology; D001516:Bees / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D019476:Insect Proteins / Q000378:metabolism; D007814:Larva / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D013058:Mass Spectrometry; D014442:Monophenol Monooxygenase / Q000378:metabolism; D040901:Proteomics
D019476:Insect Proteins; D014442:Monophenol Monooxygenase
Arch Insect Biochem Physiol. 2008 Dec;69(4):155-67
18979500
Mol Cell Proteomics. 2006 Dec;5(12):2252-62
16920818
J Invertebr Pathol. 2004 Feb;85(2):105-11
15050840
Exerc Immunol Rev. 2003;9:25-33
14686091
Genome Biol. 2008 Oct 29;9(10):R156
18959778
Environ Microbiol. 2008 Jun;10(6):1612-20
18331334
Nature. 1974 Oct 18;251(5476):610-3
4214166
J Econ Entomol. 2004 Jun;97(3):752-6
15279248
J Biol Chem. 1993 Apr 5;268(10):7044-54
8463238
Chemotherapy. 2006;52(3):158-60
16636539
Crit Rev Microbiol. 2003;29(3):191-214
14582617
Immunol Rev. 2004 Apr;198:116-26
15199959
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D192-6
15608175
Physiol Behav. 2007 Sep 10;92(1-2):256-62
17582445
J Nurs Staff Dev. 1991 Jul-Aug;7(4):196-200
1875272
Annu Rev Biochem. 1965;34:595-634
14321181
J Insect Physiol. 2004 Aug;50(8):687-94
15288202
Insect Mol Biol. 2006 Oct;15(5):645-56
17069638
Insect Biochem Mol Biol. 2005 Jun;35(6):541-52
15857760
Cell Biol Int. 1998;22(2):137-44
9878101
Cell. 2006 Apr 7;125(1):187-99
16615899
Science. 2000 Nov 10;290(5494):1166-8
11073456
Infect Immun. 2006 Jul;74(7):3693-706
16790742
Mol Pathol. 2002 Aug;55(4):209-13
12147708