Neutrophils enhance early Trypanosoma brucei infection onset

Abstract

In this study, Trypanosoma brucei was naturally transmitted to mice through the bites of infected Glossina morsitans tsetse flies. Neutrophils were recruited rapidly to the bite site, whereas monocytes were attracted more gradually. Expression of inflammatory cytokines (il1b, il6), il10 and neutrophil chemokines (cxcl1, cxcl5) was transiently up-regulated at the site of parasite inoculation. Then, a second influx of neutrophils occurred that coincided with the previously described parasite retention and expansion in the ear dermis. Congenital and experimental neutropenia models, combined with bioluminescent imaging, indicate that neutrophils do not significantly contribute to dermal parasite control and elicit higher systemic parasitemia levels during the infection onset. Engulfment of parasites by neutrophils in the skin was rarely observed and was restricted to parasites with reduced motility/viability, whereas live parasites escaped phagocytosis. To our knowledge, this study represents the first description of a trypanosome infection promoting role of early innate immunological reactions following an infective tsetse fly bite. Our data indicate that the trypanosome is not hindered in its early development and benefits from the host innate responses with the neutrophils being important regulators of the early infection, as already demonstrated for the sand fly transmitted Leishmania parasite.

Trypanosoma brucei brucei causes a rapid and persistent influx of neutrophils in the spleen of infected mice

“…In contrast, neutrophils can play a role in the establishment and persistence of the parasite infection. A recent study revealed that the rapid recruitment of neutrophils to the dermal bite site of T b brucei infected tsetse flies, did contribute to higher systematic parasitemia levels during the onset of infection …”

“…Single-cell spleen suspensions were prepared at 0, 4,5,6,7,8,9,10,14,17,21,24 and 28 days post-infection (dpi) as previously described. 13 Unless otherwise stated, cell suspensions were re-suspended in 0.05% FBS BD FACSFlow Sheath Fluid.…”

“…Upon arrival at the site of inflammation, neutrophils engage their effector functions by eliminating invading pathogens and trigger inflammatory reactions . However, recent data demonstrate that neutrophils can also extend their functions beyond their role in pathogen clearance and can play a role in promoting parasite survival, in particular, during the onset of tsetse‐transmitted trypanosomosis . The lack of systematic data on quantitative changes in spleen cell numbers throughout infection prompted the data collection reported here.…”

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

“…One obvious cellular player than comes to mind when considering dermal immunology is the presence of neutrophils. Surprisingly, a recent study addressing the role of these innate cells during the onset of infection has shown that they have an infectionenhancing effect, rather than an inhibitory function (27). While the functional role of these cells has not been addressed in other immune sites, their cell number increases dramatically in the spleen of trypanosome infected mice (28).…”

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

“…While Plasmodium sporozoites reach the draining LN in the first hour after inoculation in the skin (Amino et al, 2006) African trypanosomes take longer as the first parasites are detected in LN 18 h after infection with tsetse flies (Caljon et al, 2016). IVM studies revealed that engulfment of trypanosomes by neutrophils at the inoculation site was rarely observed and was restricted to parasites with reduced motility/viability whereas live parasites escape phagocytosis (Caljon et al, 2018) (Fig. 2Cii IVM studies combined with flow cytometry showed that Leishmania mexicana use neutrophils as a safe transient shelter and that this impacts parasite-specific immune response in mice.…”