Role of goblet cell protein CLCA1 in murine DSS colitis

Background The secreted goblet cell protein CLCA1 (chloride channel regulator, calcium-activated-1) is, in addition to its established role in epithelial chloride conductance regulation, thought to act as a multifunctional signaling protein, including cellular differentiation pathways and induction of mucus production. Specifically, CLCA1 has recently been shown to modulate early immune responses by regulation of cytokines. Here, we analyze the role of CLCA1, which is highly expressed and secreted by colon goblet cells, in the course of murine dextran sodium sulfate-induced colitis. Findings We compared Clca1-deficient and wild type mice under unchallenged and DSS-challenged conditions at various time points, including weight loss, colon weight-length- ratio and histological characterization of inflammation and regeneration. Expression levels of relevant cytokines, trefoil factor 3 and E-cadherin were assessed via quantitative PCR and cytometric bead arrays. Lack of CLCA1 was associated with a more than two-fold increased expression of Cxcl-1- and Il-17-mRNA during DSS colitis. However, no differences were found between Clca1-deficient and wild type mice under unchallenged or DSS-challenged conditions in terms of clinical findings, disease progression, colitis outcome, epithelial defects or regeneration. Conclusions CLCA1 is involved in the modulation of cytokine responses in the colon, albeit differently than what had been observed in the lungs. Obviously, the pathways involved depend on the type of challenge, time point or tissue environment

The ecology and feeding behavior of mosquitoes in the Galapagos Islands

Mosquitoes remain important vectors in transmitting wildlife diseases. This dissertation aims to understand the role that mosquitoes play in transmitting wildlife diseases such as avian malaria, a protozoan parasite belonging to the genus Plasmodium. Using data from wild-caught mosquitoes captured in multiple years and across multiple islands on the Galapagos Archipelago, we describe distributional patterns of mosquitoes, their range limits and assess whether there exists a disease-free refuge as occurs in Hawaii. We show that altitudinal ranges for disease transmission of avian malaria may not be bounded by a stable disease-free refuge, since mosquitoes are found at all elevations, and the highest peaks are significantly lower in Galapagos than in Hawaii. Secondly, we investigate the influence of ecological factors on the distribution and abundance of mosquitoes on the inhabited island of Isla Santa Cruz. We show that both Aedes taeniorhynchus and Culex quinquefasciatus, two of the three mosquito species found in Galapagos, decline with elevation. We also show the influence of statistically significant factors of elevation, temperature, and humidity on mosquitoes in Galapagos. This chapter discusses the ecological requirements of the avian malarial parasite and how this may influence disease dynamics in the Galapagos; sampling sites at all elevations were within the optimal temperature range for both mosquito and parasite development. Thirdly, using data from wild-caught mosquitoes from Santa Cruz, we discuss the feeding range of both A. taeniorhynchus and C. quinquefasciatus. This chapter takes a molecular approach in screening mosquito bloodmeals using vertebrate universal primers. Fourthly, we use a combination of field captured mosquitoes, molecular screening, and microscopy in identifying Plasmodium parasites and understanding their competence in the disease dynamics of avian malaria in Galapagos. Collectively, these results aim to guide conservation efforts towards managing disease-transmitting mosquito vectors in Galapagos