Comparison of immune responses to Loa loa stage-specific antigen extracts in Loa loa-exposed BALB/c mice upon clearance of infection

Parasit Vectors. 2020 Feb 7;13(1):51. doi: 10.1186/s13071-020-3921-x.

Abstract

Background: Different immune mechanisms are capable of killing developmental stages of filarial nematodes and these mechanisms are also likely to vary between the primary and a challenge infection. However, the lack of a detailed analysis of cytokine, chemokine and immunoglobulin levels in human loiasis is still evident. Therefore, detailed analysis of immune responses induced by the different developmental stages of Loa loa in immune-competent BALB/c mice will aid in the characterization of distinct immune responses that are important for the immunity against loiasis.

Methods: Different developmental stages of L. loa were obtained from human peripheral blood (microfilariae, MF), the transmitting vector, Chrysops (larval stage 3, L3) and infected immune-deficient BALB/cRAG2γc-/- mice (L4, L5, adult worms). Groups of wildtype BALB/c mice were then injected with the isolated stages and after 42 days post-infection (pi), systemic cytokine, chemokine and immunoglobulin levels were determined. These were then compared to L. loa-specific responses from in vitro re-stimulated splenocytes from individual mice. All parameters were determined using Luminex technology.

Results: In a pilot study, BALB/c mice cleared the different life stages of L. loa within 42 days pi and systemic cytokine, chemokine and immunoglobulin levels were equal between infected and naive mice. Nevertheless, L. loa-specific re-stimulation of splenocytes from mice infected with L5, MF or adult worms led to induction of Th2, Th17 and chemokine secretion patterns.

Conclusions: This study shows that although host immunity remains comparable to naive mice, clearance of L. loa life-cycle development stages can induce immune cell memory leading to cytokine, chemokine and immunoglobulins secretion patterns which might contribute to immunity and protection against reinfection.

Keywords: Adult worms; Chemokines; Cytokines; Immunoglobulins; Larvae; Loa loa antigen extract; Microfilariae; Re-stimulation; Recall immune responses.

MeSH terms

  • Animals
  • Antigens, Helminth / blood
  • Cytokines / blood
  • Diptera / parasitology
  • Humans
  • Immunity, Humoral*
  • Immunoglobulins / blood
  • Insect Vectors / parasitology
  • Larva / parasitology
  • Life Cycle Stages / immunology*
  • Loa / immunology*
  • Loiasis / immunology*
  • Mice
  • Mice, Inbred BALB C / immunology*
  • Mice, Inbred BALB C / parasitology
  • Neglected Diseases / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Antigens, Helminth
  • Cytokines
  • Immunoglobulins