Cellular Immunology Lab

About the lab

Research in the Cellular Immunology Lab is focused on understanding the cellular immune response, and the tricks that pathogens and parasites use to overcome it. For this research we utilize the Drosophila melanogaster-parasitoid wasp host-parasite system. The fruit fly Drosophila melanogaster provides an excellent model to gain insight into the immune responses of humans and other insects including mosquitoes, which transmit human disease, and diverse bee species, which are important agricultural pollinators.

Featured research (5)

Immune self-tolerance is the ability of a host's immune system to recognize and avoid triggering immune responses against self-tissue. This allows the host to avoid self-directed immune damage while still responding appropriately to pathogen infection. A breakdown of self-tolerance can lead to an autoimmune state in which immune cells target healthy self-tissue, leading to inflammation and tissue damage. In order to better understand the basic biology of autoimmunity and the role of the innate immune system in maintaining self-tolerance, we have recently characterized the Drosophila melanogaster tuSz autoimmune mutant. This mutant strain can serve as a model of innate immune mediated self-tolerance, and here we identify transcripts that are deregulated in flies experiencing a loss of self-tolerance. We found that these changes include the ectopic activation of pro-inflammatory signaling through the Relish/NFκB transcription factor, alterations in transcripts encoding proteins predicted to mediate organismal metabolism, and a downregulation of transcripts linked to developmental processes. This study can provide insight into the transcriptional and physiological changes underlying self-tolerance and autoimmunity.
In order to respond to infection, hosts must distinguish pathogens from their own tissues. This allows for the precise targeting of immune responses against pathogens and also ensures self-tolerance, the ability of the host to protect self tissues from immune damage. One way to maintain self-tolerance is to evolve a self signal and suppress any immune response directed at tissues that carry this signal. Here, we characterize the Drosophila tuSz 1 mutant strain, which mounts an aberrant immune response against its own fat body. We demonstrate that this autoimmunity is the result of two mutations: 1) a mutation in the GCS1 gene that disrupts N-glycosylation of extracellular matrix proteins covering the fat body, and 2) a mutation in the Drosophila Janus Kinase ortholog that causes precocious activation of hemocytes. Our data indicate that N-glycans attached to extracellular matrix proteins serve as a self signal and that activated hemocytes attack tissues lacking this signal. The simplicity of this invertebrate self-recognition system and the ubiquity of its constituent parts suggests it may have functional homologs across animals.
The interactions between Drosophila melanogaster and the parasitoid wasps that infect Drosophila species provide an important model for understanding host–parasite relationships. Following parasitoid infection, D. melanogaster larvae mount a response in which immune cells (hemocytes) form a capsule around the wasp egg, which then melanizes, leading to death of the parasitoid. Previous studies have found that host hemocyte load; the number of hemocytes available for the encapsulation response; and the production of lamellocytes, an infection induced hemocyte type, are major determinants of host resistance. Parasitoids have evolved various virulence mechanisms to overcome the immune response of the D. melanogaster host, including both active immune suppression by venom proteins and passive immune evasive mechanisms. We identified a previously undescribed parasitoid species, Asobara sp. AsDen, which utilizes an active virulence mechanism to infect D. melanogaster hosts. Asobara sp. AsDen infection inhibits host hemocyte expression of msn, a member of the JNK signaling pathway, which plays a role in lamellocyte production. Asobara sp. AsDen infection restricts the production of lamellocytes as assayed by hemocyte cell morphology and altered msn expression. Our findings suggest that Asobara sp. AsDen infection alters host signaling to suppress immunity.
In nature, larvae of the fruit fly Drosophila melanogaster are commonly infected by parasitoid wasps. Following infection, flies mount an immune response termed cellular encapsulation in which fly immune cells form a multilayered capsule that covers and kills the wasp egg. Parasitoids have thus evolved virulence factors to suppress cellular encapsulation. To uncover the molecular mechanisms underlying the anti-wasp response, we and others have begun identifying and functionally characterizing these virulence factors. Our recent work on the Drosophila parasitoid Ganaspis sp1 has demonstrated that a virulence factor encoding a SERCA-type calcium pump plays an important role in Ganaspis sp1 virulence. The SERCA venom antagonizes fly immune cell calcium signaling and thereby prevents the activation of the encapsulation response. In this way, the study of wasp virulence factors has revealed a novel aspect of fly immunity, namely a role for calcium signaling in fly immune cell activation, which is conserved with human immunity, again illustrating the marked conservation between fly and mammalian immune responses. Our findings demonstrate that the cellular encapsulation response can serve as a model of immune cell function and can also provide valuable insight into basic cell biological processes.
Because parasite virulence factors target host immune responses, identification and functional characterization of these factors can provide insight into poorly understood host immune mechanisms. The fruit fly Drosophila melanogaster is a model system for understanding humoral innate immunity, but Drosophila cellular innate immune responses remain incompletely characterized. Fruit flies are regularly infected by parasitoid wasps in nature and, following infection, flies mount a cellular immune response culminating in the cellular encapsulation of the wasp egg. The mechanistic basis of this response is largely unknown, but wasps use a mixture of virulence proteins derived from the venom gland to suppress cellular encapsulation. To gain insight into the mechanisms underlying wasp virulence and fly cellular immunity, we used a joint transcriptomic/proteomic approach to identify venom genes from Ganaspis sp.1 (G1), a previously uncharacterized Drosophila parasitoid species, and found that G1 venom contains a highly abundant sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. Accordingly, we found that fly immune cells termed plasmatocytes normally undergo a cytoplasmic calcium burst following infection, and that this calcium burst is required for activation of the cellular immune response. We further found that the plasmatocyte calcium burst is suppressed by G1 venom in a SERCA-dependent manner, leading to the failure of plasmatocytes to become activated and migrate toward G1 eggs. Finally, by genetically manipulating plasmatocyte calcium levels, we were able to alter fly immune success against G1 and other parasitoid species. Our characterization of parasitoid wasp venom proteins led us to identify plasmatocyte cytoplasmic calcium bursts as an important aspect of fly cellular immunity.

Lab head

Nathan T Mortimer
  • School of Biological Sciences
About Nathan T Mortimer
  • My research is focused on uncovering the mechanisms that determine the outcome of infection in host-parasite interactions, using a Drosophila melanogaster-parasitoid wasp model host-parasite system. In this research I take an integrative approach, in which I use molecular genetics, genomics and bioinformatic techniques to investigate the molecular basis of the interactions between host immune responses and parasite virulence factors.

Members (3)

Ashley L Waring
  • Illinois State University
Susana Calderon
  • Illinois State University
Elise Nguyen Le
  • Illinois State University

Alumni (3)

Chris Lark
  • Illinois State University
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Ewurabena Okai
  • Illinois State University