CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality

Ramesh P. Thylur, Xianzhu Wu, Nagaraj M. Gowda, Kishore Punnath, Shivayogeeshwara E. Neelgund, Maria Febbraio, D. Channe Gowda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In malaria, CD36 plays several roles, including mediating parasite sequestration to host organs, phagocytic clearance of parasites, and regulation of immunity. Although the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and Cd36-/- mice infected with a non-lethal strain of Plasmodium yoelii. Compared with Cd36-/- mice, WT mice had lower parasitemias and were resistant to death. At early but not at later stages of infection, WT mice had higher circulatory proinflammatory cytokines and lower anti-inflammatory cytokines than Cd36-/- mice.WT mice showed higher frequencies of proinflammatory cytokineproducing and lower frequencies of anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer cells than Cd36-/- mice. Cytokines produced by co-cultures of DCs from infected mice and ovalbumin-specific, MHC class II-restricted -/- (OT-II)Tcells reflected CD36-dependentDCfunction. WT mice also showed increased Th1 and reduced Th2 responses compared with Cd36-/- mice, mainly at early stages of infection. Furthermore, in infected WT mice, macrophages and neutrophils expressed higher levels of phagocytic receptors and showed enhanced phagocytosis of parasite-infected erythrocytes than those in Cd36-/- mice in an IFN-γ-dependent manner. However, there were no differences in malaria-induced humoral responses betweenWTand Cd36-/- mice. Overall, the results show that CD36 plays a significant role in controlling parasite burden by contributing to proinflammatory cytokine responses by DCs and natural killer cells, Th1 development, phagocytic receptor expression, and phagocytic activity.

Original languageEnglish (US)
Pages (from-to)9394-9408
Number of pages15
JournalJournal of Biological Chemistry
Volume292
Issue number22
DOIs
StatePublished - Jun 2 2017

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Parasitemia
Malaria
Blood
Mortality
Cytokines
Infection
Parasites
Anti-Inflammatory Agents
Dendritic Cells
Immunity
Macrophages
Ovalbumin
Phagocytosis
Natural Killer Cells
Plasmodium yoelii
Adaptive Immunity
Coculture Techniques
Innate Immunity
Neutrophils

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Thylur, Ramesh P. ; Wu, Xianzhu ; Gowda, Nagaraj M. ; Punnath, Kishore ; Neelgund, Shivayogeeshwara E. ; Febbraio, Maria ; Channe Gowda, D. / CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 22. pp. 9394-9408.
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abstract = "In malaria, CD36 plays several roles, including mediating parasite sequestration to host organs, phagocytic clearance of parasites, and regulation of immunity. Although the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and Cd36-/- mice infected with a non-lethal strain of Plasmodium yoelii. Compared with Cd36-/- mice, WT mice had lower parasitemias and were resistant to death. At early but not at later stages of infection, WT mice had higher circulatory proinflammatory cytokines and lower anti-inflammatory cytokines than Cd36-/- mice.WT mice showed higher frequencies of proinflammatory cytokineproducing and lower frequencies of anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer cells than Cd36-/- mice. Cytokines produced by co-cultures of DCs from infected mice and ovalbumin-specific, MHC class II-restricted -/- (OT-II)Tcells reflected CD36-dependentDCfunction. WT mice also showed increased Th1 and reduced Th2 responses compared with Cd36-/- mice, mainly at early stages of infection. Furthermore, in infected WT mice, macrophages and neutrophils expressed higher levels of phagocytic receptors and showed enhanced phagocytosis of parasite-infected erythrocytes than those in Cd36-/- mice in an IFN-γ-dependent manner. However, there were no differences in malaria-induced humoral responses betweenWTand Cd36-/- mice. Overall, the results show that CD36 plays a significant role in controlling parasite burden by contributing to proinflammatory cytokine responses by DCs and natural killer cells, Th1 development, phagocytic receptor expression, and phagocytic activity.",
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CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality. / Thylur, Ramesh P.; Wu, Xianzhu; Gowda, Nagaraj M.; Punnath, Kishore; Neelgund, Shivayogeeshwara E.; Febbraio, Maria; Channe Gowda, D.

In: Journal of Biological Chemistry, Vol. 292, No. 22, 02.06.2017, p. 9394-9408.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality

AU - Thylur, Ramesh P.

AU - Wu, Xianzhu

AU - Gowda, Nagaraj M.

AU - Punnath, Kishore

AU - Neelgund, Shivayogeeshwara E.

AU - Febbraio, Maria

AU - Channe Gowda, D.

PY - 2017/6/2

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N2 - In malaria, CD36 plays several roles, including mediating parasite sequestration to host organs, phagocytic clearance of parasites, and regulation of immunity. Although the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and Cd36-/- mice infected with a non-lethal strain of Plasmodium yoelii. Compared with Cd36-/- mice, WT mice had lower parasitemias and were resistant to death. At early but not at later stages of infection, WT mice had higher circulatory proinflammatory cytokines and lower anti-inflammatory cytokines than Cd36-/- mice.WT mice showed higher frequencies of proinflammatory cytokineproducing and lower frequencies of anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer cells than Cd36-/- mice. Cytokines produced by co-cultures of DCs from infected mice and ovalbumin-specific, MHC class II-restricted -/- (OT-II)Tcells reflected CD36-dependentDCfunction. WT mice also showed increased Th1 and reduced Th2 responses compared with Cd36-/- mice, mainly at early stages of infection. Furthermore, in infected WT mice, macrophages and neutrophils expressed higher levels of phagocytic receptors and showed enhanced phagocytosis of parasite-infected erythrocytes than those in Cd36-/- mice in an IFN-γ-dependent manner. However, there were no differences in malaria-induced humoral responses betweenWTand Cd36-/- mice. Overall, the results show that CD36 plays a significant role in controlling parasite burden by contributing to proinflammatory cytokine responses by DCs and natural killer cells, Th1 development, phagocytic receptor expression, and phagocytic activity.

AB - In malaria, CD36 plays several roles, including mediating parasite sequestration to host organs, phagocytic clearance of parasites, and regulation of immunity. Although the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and Cd36-/- mice infected with a non-lethal strain of Plasmodium yoelii. Compared with Cd36-/- mice, WT mice had lower parasitemias and were resistant to death. At early but not at later stages of infection, WT mice had higher circulatory proinflammatory cytokines and lower anti-inflammatory cytokines than Cd36-/- mice.WT mice showed higher frequencies of proinflammatory cytokineproducing and lower frequencies of anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer cells than Cd36-/- mice. Cytokines produced by co-cultures of DCs from infected mice and ovalbumin-specific, MHC class II-restricted -/- (OT-II)Tcells reflected CD36-dependentDCfunction. WT mice also showed increased Th1 and reduced Th2 responses compared with Cd36-/- mice, mainly at early stages of infection. Furthermore, in infected WT mice, macrophages and neutrophils expressed higher levels of phagocytic receptors and showed enhanced phagocytosis of parasite-infected erythrocytes than those in Cd36-/- mice in an IFN-γ-dependent manner. However, there were no differences in malaria-induced humoral responses betweenWTand Cd36-/- mice. Overall, the results show that CD36 plays a significant role in controlling parasite burden by contributing to proinflammatory cytokine responses by DCs and natural killer cells, Th1 development, phagocytic receptor expression, and phagocytic activity.

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