Allergen-triggered airway hyperresponsiveness and lung pathology in mice sensitized with the biopesticide Metarhizium anisopliae

Metarhizium anisopliae is an entomopathogenic fungus recently licensed for indoor control of cockroaches, a major source of allergens. While M. anisop liae has been shown to be non-infectious and non-toxic to mammals there has been only limited research on potential allergenicity. Using a mouse model , we previously demonstrated allergic immune and inflammatory responses to this agent. The present study was designed to determine whether these respo nses were associated with changes in pulmonary responses, lung pathology, a nd the cytokine profile in bronchoalveolar lavage fluid (BALF). Soluble fac tors from fungal components were combined in equal protein amounts to form M. anisopliae crude antigen (MACA). BALB/C mice were intratracheally (IT) c hallenged with 10 mu g MACA 14 days post intraperitoneal sensitization with 25 mu g fungal antigen in aluminum hydroxide adjuvant. Physiological and c ellular changes were examined. The mice were tested for airway hyperrespons iveness before (No Chal) and after (1, 3, and 8 days post challenge (DPIT)) MACA IT challenge. Subsequently, serum, BALF and the lungs were harvested. All treatment groups concurrently demonstrated significant non-specific pu lmonary inflammation (neutrophil influx) and increased pulmonary sensitivit y to methacholine (Mch) at 1 DPIT MACA challenge. Where as both adjuvant tr eated and naive mice airway responses had returned to near normal levels by 3 DPIT, mice which were previously sensitized with MACA wore still hyperre sponsive to Mch challenge at 3 and 8 DPIT. This hyperresponsiveness correla tes with eosinophil and lymphocyte influx, which is maximal at 3 DPIT and s till elevated at 8 DPIT. Interleukin (IL) 5 was elevated for all treatment groups at 1 DPIT but only the MACA sensitized mice maintained elevated leve ls for both 3 and 8 DPIT. Furthermore, MACA sensitized mice had a more exte nsive inflammatory histopathology at all examined time points with peribron chial and perivascular infiltrates, like those associated with allergic res ponsiveness, peaking at 3 DPIT. These pulmonary pathologic changes appeared to be consistent with elevated levels of serum and BALF total IgE, BALF IL -4, eosinophils. and lymphocytes: following MACA IT challenge in MACA sensi tized mice. There were no significant differences among the: three treatmen t groups with regard to BALF interferon (IFN) gamma. The cytokines profiled indicate a Th2-type response, which is reflected in the cellular influx an d total IgE induction. These data further indicate that immune inflammatory responses, observed in mice following MACA sensitization and challenge, ar e associated with physiologic changes and histopathology characteristic of allergic disease. (C) 2000 Published by Elsevier Science ireland Ltd. All r ights reserved.