Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

Abstract

BackgroundIn invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS) after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR), which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand.MethodsRecombinant HmC1q (rHmC1q) was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques.ResultsrHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia.ConclusionsA previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal leech.

Calreticulin contributes to C1q-dependent recruitment of microglia in the leech Hirudo medicinalis following a CNS injury

“…In the leech CNS, Hm C1q contributes to the microglial recruitment by interacting with a recently characterized receptor, named Hm C1qBP, which is homologous to mammalian gC1qR [26]. The present report shows the involvement of a second receptor in the C1q-dependent microglial activation.…”

“…We also reported that Hm C1q exerts its chemotactic functions on leech microglia by recognizing at least one receptor homologous to human gC1qR (C1qBP) [26]. …”

The Leech Nervous System: A Valuable Model to Study the Microglia Involvement in Regenerative Processes

“…The production of the recombinant form of Hm C1q permitted specifying its importance in the microglia migration into the connectives [74]. As discussed above, ex vivo experiments can be performed on the isolated segment of nerve cord maintained in tissue culture.…”

“…Then, the existence of a receptor for Hm C1q (called Hm gC1qR or Hm C1qBP) in the leech CNS has been demonstrated following its molecular characterization from leech databases [74]. The involvement of Hm C1qBP in Hm C1q-dependent chemotaxis has been definitely ascertained showing the inhibition of Hm C1q effect on in vitro leech microglia migration by using anti-C1qBP antibodies.…”

C1QBP is upregulated in colon cancer and binds to apolipoprotein A-I

“…C1QBP is commonly localized in the mitochondrial matrix, although it exhibits differential localization among cell lines under various physiological conditions (1). Moreover, it serves important roles in various biological processes, including inflammation, infection, cell signaling and chemotaxis (2)(3)(4).…”