Chemical modulators of the innate immune response alter gypsy moth larval susceptibility to Bacillus thuringiensis

Abstract

BackgroundThe gut comprises an essential barrier that protects both invertebrate and vertebrate animals from invasion by microorganisms. Disruption of the balanced relationship between indigenous gut microbiota and their host can result in gut bacteria eliciting host responses similar to those caused by invasive pathogens. For example, ingestion of Bacillus thuringiensis by larvae of some species of susceptible Lepidoptera can result in normally benign enteric bacteria exerting pathogenic effects.ResultsWe explored the potential role of the insect immune response in mortality caused by B. thuringiensis in conjunction with gut bacteria. Two lines of evidence support such a role. First, ingestion of B. thuringiensis by gypsy moth larvae led to the depletion of their hemocytes. Second, pharmacological agents that are known to modulate innate immune responses of invertebrates and vertebrates altered larval mortality induced by B. thuringiensis. Specifically, Gram-negative peptidoglycan pre-treated with lysozyme accelerated B. thuringiensis-induced killing of larvae previously made less susceptible due to treatment with antibiotics. Conversely, several inhibitors of the innate immune response (eicosanoid inhibitors and antioxidants) increased the host's survival time following ingestion of B. thuringiensis.ConclusionsThis study demonstrates that B. thuringiensis infection provokes changes in the cellular immune response of gypsy moth larvae. The effects of chemicals known to modulate the innate immune response of many invertebrates and vertebrates, including Lepidoptera, also indicate a role of this response in B. thuringiensis killing. Interactions among B. thuringiensis toxin, enteric bacteria, and aspects of the gypsy moth immune response may provide a novel model to decipher mechanisms of sepsis associated with bacteria of gut origin.

Midgut microbiota and host immunocompetence underlieBacillus thuringiensiskilling mechanism

“…A heated debate on the B. thuringiensis killing mechanism started almost a decade ago, and a consensus has not yet been reached. Indeed, divergent opinions persist on the role played by the microbiota residing in the midgut of lepidopteran hosts and the septicemia it may cause after toxin-induced disruption of the lining epithelium (22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Whether the gut paralysis and associated feeding cessation observed in larvae exposed to Cry pore-forming toxins or the septicemia induced by bacterial proliferation in the insect body cavity is the major factor contributing to eventual death remains to be resolved (5,32) Significance Bacillus thuringiensis and its toxins are widely used for insect control.…”

“…To circumvent the problems associated with the manipulation of the midgut microbiota with antibiotics (22)(23)(24)(25)(27)(28)(29)(30)(31) or of the immune response with immunosuppressive molecules (26,34), both of which have unpredictable multiple effects, we performed selective RNAi-mediated silencing of an immune gene (102 Sl, 102 Spodoptera littoralis), recently identified in Spodoptera littoralis (35). This gene is highly expressed in the immune cells circulating in the hemolymph (i.e., hemocytes) and modulates their incorporation in multilayered capsules formed around foreign intruders entering the body cavity (i.e., the hemocoel) (35).…”

More wrinkles to Bt susceptibility

“…Nearly a decade ago we presented a new model proposing that in in some, but not all, lepidopteran species Bt and its insecticidal toxin acted in concert with enteric bacteria to account for the final death of insect larvae, and that alteration of the host innate immune responses might contribute to this linkage. [10][11][12] This model launched a heated debate in the field, as others showed that while elimination of the gut microbiota by antibiotic feeding could reduce susceptibility, the mechanism of gut microbiota suppression was due to a direct effect of antibiotics on the Bt toxin. [13][14][15] More recently, a number of studies, including this issues' paper and previous work from Dubovskiy and colleagues 16 have described impacts of Bt on the microbiome and contributions of microbiota and the immune response to host susceptibility.…”

Immunomodulation in insects post-treatment with abiotic agents: A review

“…While the immunomodulatory mechanisms of antibiotics are not fully understood, there is evidence that some directly reduce the activity of the host's immune system, whereas others limit the release of immunobacterial components (Tauber & Nau, 2008). Broderick et al (2010) explored the potential role of the immune response of gypsy moth larvae, Lymnatria dispar, in mortality caused by B. thuringiensis in conjunction with gut bacteria. Two lines of evidence support such role.…”