Pathological roles of MRP14 in anemia and splenomegaly during experimental visceral leishmaniasis

PLoS Negl Trop Dis. 2020 Jan 21;14(1):e0008020. doi: 10.1371/journal.pntd.0008020. eCollection 2020 Jan.

Abstract

Myeloid-related protein 14 (MRP14) belongs to the S100 calcium-binding protein family and is expressed in neutrophils and inflammatory macrophages. Increase in the number of MRP14+ cells or serum level of MRP14 is associated with various diseases such as autoimmune diseases and infectious diseases, suggesting the involvement of the molecule in pathogenesis of those diseases. In this study, to examine the pathological involvement of MRP14 during cutaneous and visceral leishmaniasis, wild-type (WT) and MRP14 knockout (MRP14KO) mice were infected with Leishmania major and L. donovani. Increase in the number of MRP14+ cells at the infection sites in wild-type mice was commonly found in the skin during L. major infection as well as the spleen and liver during L. donovani infection. In contrast, the influence of MRP14 to the pathology seemed different between the two infections. MRP14 depletion exacerbated the lesion development and ulcer formation in L. major infection. On the other hand, the depletion improved anemia and splenomegaly but not hepatomegaly at 24 weeks of L. donovani infection. These results suggest that, distinct from its protective role in CL, MRP14 is involved in exacerbation of some symptoms during VL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / genetics
  • Anemia / metabolism*
  • Anemia / parasitology
  • Anemia / pathology*
  • Animals
  • Calgranulin B / genetics
  • Calgranulin B / metabolism*
  • Female
  • Humans
  • Leishmania donovani / physiology
  • Leishmania major / physiology
  • Leishmaniasis, Visceral / genetics
  • Leishmaniasis, Visceral / metabolism*
  • Leishmaniasis, Visceral / parasitology
  • Leishmaniasis, Visceral / pathology*
  • Liver / metabolism
  • Liver / parasitology
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Spleen / metabolism
  • Spleen / parasitology
  • Spleen / pathology
  • Splenomegaly / genetics
  • Splenomegaly / metabolism*
  • Splenomegaly / parasitology
  • Splenomegaly / pathology*

Substances

  • Calgranulin B
  • S100A9 protein, mouse

Grant support

This work was supported by KAKENHI (15J08617 to HM, No. 26712025 to WF, 17J06910 to AM, No. 16K15051 and 18H02649 to YG) from Japan Society for the Promotion of Science (https://www.jsps.go.jp/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.