Analysis of theCaenorhabditis elegansinnate immune response toCoxiella burnetii

Abstract

The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan. However, nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although vertebrates detect C. burnetii via TLRs, pathologies in tol-1(−) mutant nematodes were indistinguishable from N2, and indicate nematodes do not employ this orthologue for detection of C. burnetii. sek-1(−) MAP kinase mutant nematodes succumbed to infection faster, suggesting that this signaling pathway plays a role in immune activation, as previously shown for orthologues in vertebrates during a C. burnetii infection. C. elegans daf-2(−) mutants are hyper-immune and exhibited significantly reduced pathological consequences during challenge. Collectively, these results demonstrate the utility of C. elegans for studying the innate immune response against C. burnetii and could lead to discovery of novel methods for prevention and treatment of disease in humans and livestock.

Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection

“…Our results using Drosophila corroborated relevant aspects of Coxiella infection previously shown in G. mellonella, C. elegans, and tick cells (24)(25)(26), such as CCV formation and the role of the T4SS in replication in an arthropod model. Using adult flies, we were able to demonstrate that the Drosophila TNF homolog, Eiger, is implicated in susceptibility to infection.…”

“…Other animal and avirulent bacterial models, particularly those suitable for BSL2, represent safer alternatives to investigate how host and bacterial factors interface and affect the pathogenesis of C. burnetii. Here, we present Drosophila as a genetically tractable host model to study Coxiella infection that complements previous work performed in mammalian and other invertebrate models (23)(24)(25). The malleability of the C. elegans and Drosophila models makes them applicable to studies in mammalian systems, and Drosophila can be used to identify novel arthropod genetic variants implicated in susceptibility to C. burnetii infection that have homologous mammalian counterparts.…”

“…Another study used larvae of the greater wax moth, Galleria mellonella, to investigate antibiotic efficacy following Coxiella infection and the role of dotA/dotB, two components of the Coxiella T4SS, in establishing infection (24). The wax moth model revealed relevant information on antimicrobials and Coxiella biology in arthropods; however, this host system lacks the genetic malleability found in other models, such the recently described Caenorhabditis elegans nematode model (25) or the arthropod Drosophila melanogaster. Thus, a genetically tractable arthropod model that supports Coxiella replication would be useful in addressing the host immune response induced by Coxiella infection and the bacterial factors implicated in the formation of the Coxiella-containing vacuole (CCV) leading to the establishment of infection.…”

Global Proteomics Revealed Klebsiella pneumoniae Induced Autophagy and Oxidative Stress in Caenorhabditis elegans by Inhibiting PI3K/AKT/mTOR Pathway during Infection

“…Hence, the C. elegans , which is devoid of lungs system, has globally been accepted as a suitable model (Singh and Aballay, 2006 ; Akira, 2009 ) to study host response against lung and respiratory tract infecting microorganisms such as P. aeruginosa (Tan et al, 1999 ; Kirienko et al, 2013 ; Balasubramanian et al, 2016 ), Streptococcus pneumoniae (Bolm et al, 2004 ), Streptococcus pyogens (Jansen et al, 2002 ), Microbacterium Spp. (Hodgkin et al, 2000 ), Mycoplasma iowae (Pritchard et al, 2014 ), S. aureus (Bogaerts et al, 2010a ; JebaMercy et al, 2011 ), Legionella pneumoniae (Brassinga et al, 2010 ; Komura et al, 2010 ; Hellinga et al, 2015 ), Coxiella burnetti (Battisti et al, 2017 ), and Mycobacterium tuberculosis (Galbadage et al, 2016 ). In addition, a study by Green et al ( 2009 ) utilized C. elegans to characterize the impact of cigarette smoke on innate immune response of host fortifies the idea of using nematode as lung and respiratory disease model.…”

Global Transcriptome Changes That Accompany Alterations in Serotonin Levels inCaenorhabditis elegans

“…Among the genes that displayed the largest upregulation were T07F10.1 (anp-1) a poorly-characterized aminopeptidase ortholog of mammalian endoplasmic reticulum aminopeptidase (ERAP1), and ERAP2 (endoplasmic reticulum aminopeptidase 2), that by analogy to its role in other nematodes, could play roles in digestion, metabolite excretion, neuropeptide processing and/or osmotic regulation (Davey and Sommerville 1974), fbxb-19, K10G4.10 and fbxa-103 three of the 326 predicted F-box containing proteins in C. elegans (Kipreos and Pagano 2000) and genes predicted to encode proteins that were either transcription factors, or had DNA binding activity. Among the downregulated genes we found those that encode proteins directly involved in metabolism such as F42A10.9, an enzyme predicted to be involved in the breakdown of crosslinked proteins, gfat-2 a glucosamine-fructose-6-phosphate aminotransferase predicted to catalyze the first step in the hexosamine pathway (Ghosh et al 2014), lys-10 a lysozyme involved in longevity (Samuelson et al 2007), endu-2, an endonuclease important for stress tolerance (Ujisawa et al 2018;Battisti et al 2017), acs-2 involved in fatty acid metabolism (Liang et al 2010;Nomura et al 2010), and asp-8, predicted to have endopeptidase activity. Thus, it appeared that the loss of 5-HT caused an overall increase in gene expression within the animal, as well as significantly downregulated genes that could alter metabolism.…”