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<p>Abstract</p> <p>Background</p> <p>Insects react against pathogens through innate immunity. The cotton bollworm <it>Helicoverpa armigera </it>(<it>H. armigera</it>) is an important defoliator and an extremely destructive pest insect of many crops. The elucidation of the mechanism of the immune response of <it>H. armigera </it>to various pathogens can provide a theoretical basis for new approaches to biologically control this pest.</p> <p>Results</p> <p>Four kinds of pathogens <it>Bacillus thuringiensis</it>, <it>Klebsiella pneumoniae</it>, <it>Candida albicans</it>, and <it>Autographa californica </it>multiple nucleocapsid nucleopolyhedrovirus harbored green fluorescence protein and polyhedron (<it>Ac</it>MNPV-GFP) were used to challenge the insect. The cellular and humoral immune responses to the pathogens were analyzed in the challenged <it>H. armigera</it>. The results show that in the five kinds of haemocytes, only granulocytes phagocytized the Gram-negative and Gram-positive bacteria and fungi. All haemocytes can be infected by <it>Ac</it>MNPV. Fourteen immune-related genes including pattern recognition receptors (PRRs) such as peptidoglycan recognition proteins (<it>HaPGRP </it>and <it>HaPGRP C</it>) and Gram-Negative Bacteria-Binding Protein (<it>HaGNBP</it>), and antimicrobial peptides (AMPs) such as <it>cecropin-1, 2 </it>and <it>3 </it>(<it>HaCec-1, 2 </it>and <it>3</it>), <it>lysozyme </it>(<it>HaLys</it>), attacin (<it>HaAtt</it>), <it>gallerimycin-like </it>(<it>HaGall</it>), <it>gloverin-like </it>(<it>HaGlo</it>), <it>moricin-like </it>(<it>HaMor</it>), cobatoxin-like (<it>HaCob</it>), <it>galiomicin-like </it>(<it>HaGali</it>), and <it>immune inducible protein </it>(<it>HaIip</it>) appeared in different expression profiles to different pathogen infections. The transcripts of 13 immune related genes (except <it>HaPGRPC</it>) are obviously up-regulated by Gram-positive bacteria. <it>HaCec-1 and 3, HaMor, HaAtt, HaLys</it>, <it>HaIip</it>, <it>HaPGRP </it>and <it>HaGNBP </it>are greatly up-regulated after fungal infection. <it>HaGNBP, HaCec-2, HaGall, HaGlo, HaMor, HaCob, HaGali </it>obviously increased in Gram-negative bacterial infection. Only five genes, <it>HaGNBP, HaCec-1</it>, <it>HaGali</it>, <it>HaGlo</it>, and <it>HaLys</it>, are weakly up-regulated after viral infection. The AMP transcripts had higher expression levels than the PRR transcripts after the microbial challenge.</p> <p>Conclusions</p> <p>These data suggest that the granulocytes are the major phagocytes in <it>H. armigera</it>. All haemocytes can be infected by <it>Ac</it>MNPV. The transcripts of 14 immune related genes have different expression patterns in <it>H. armigera </it>infected by different pathogens, which means that the immune-related genes may have different functions against various kinds of pathogens.</p>