scholarly journals S100A8/S100A9 deficiency increases neutrophil activation and protective immune responses against invading infective L3 larvae of the filarial nematode Litomosoides sigmodontis

2020 ◽  
Vol 14 (2) ◽  
pp. e0008119 ◽  
Author(s):  
Stefan J. Frohberger ◽  
Frederic Fercoq ◽  
Anna-Lena Neumann ◽  
Jayagopi Surendar ◽  
Wiebke Stamminger ◽  
...  
2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Adriana Navas ◽  
Olga Fernández ◽  
Carolina Gallego-Marín ◽  
María del Mar Castro ◽  
Mariana Rosales-Chilama ◽  
...  

ABSTRACT The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by Leishmania (Viannia) species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate. The ex vivo response of PBMCs to L. (V.) panamensis partially reflected that of lesion microenvironments. Significant downregulation of gene expression profiles consistent with local innate immune responses (monocyte and neutrophil activation and chemoattractant molecules) was observed at EoT in biopsy specimens of patients who cured (n = 8), compared to those from patients with treatment failure (n = 8). Among differentially expressed genes, pretreatment expression of CCL2 was significantly predictive of the therapeutic response (receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.82, P = 0.02). Polymorphisms in regulatory regions of the CCL2 promoter were analyzed in a pilot cohort of DNA samples from CL patients (cures, n = 20, and treatment failure, n = 20), showing putative association of polymorphisms rs13900(C/T) and rs2857656(G/C) with treatment outcome. Our data indicate that dampening gene expression profiles of monocyte and neutrophil activation characterize clinical cure after treatment of CL, supporting participation of parasite-sustained inflammation or deregulated innate immune responses in treatment failure.


Parasitology ◽  
2000 ◽  
Vol 120 (3) ◽  
pp. 271-280 ◽  
Author(s):  
L. LE GOFF ◽  
C. MARTIN ◽  
I. P. OSWALD ◽  
P. N. VUONG ◽  
G. PETIT ◽  
...  

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.


2019 ◽  
Vol 13 (11) ◽  
pp. e0007811 ◽  
Author(s):  
Juan F. Quintana ◽  
Sujai Kumar ◽  
Alasdair Ivens ◽  
Franklin W. N. Chow ◽  
Anna M. Hoy ◽  
...  

2020 ◽  
Vol 14 (7) ◽  
pp. e0008427
Author(s):  
Marc P. Hübner ◽  
Coralie Martin ◽  
Sabine Specht ◽  
Marianne Koschel ◽  
Bettina Dubben ◽  
...  

1999 ◽  
Vol 103 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Achim Hoerauf ◽  
Kerstin Nissen-Pähle ◽  
Christel Schmetz ◽  
Kim Henkle-Dührsen ◽  
Mark L. Blaxter ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jesuthas Ajendra ◽  
Sabine Specht ◽  
Sebastian Ziewer ◽  
Andrea Schiefer ◽  
Kenneth Pfarr ◽  
...  

2003 ◽  
Vol 71 (12) ◽  
pp. 6820-6829 ◽  
Author(s):  
Simon Babayan ◽  
Marie-Noëlle Ungeheuer ◽  
Coralie Martin ◽  
Tarik Attout ◽  
Elodie Belnoue ◽  
...  

ABSTRACT In order to understand natural resistance to filariasis, we compared Litomosoides sigmodontis primary infection of C57BL/6 mice, which eliminate the worms before patency, and BALB/c mice, in which worms complete their development and produce microfilariae. Our analysis over the first month of infection monitoredmigration of the infective larvae from the lymph nodes to the pleural cavity, where the worms settle. Although immune responses from the mouse strains differed from the outset, the duration of lymphatic migration (4 days) and filarial recovery rates were similar, thus confirming that the proportion of larvae that develop in the host species upon infection is not influenced by host genetic variability. The majority of worms reached the adult stage in both mouse strains; however, worm growth and molting were retarded in resistant C57BL/6 mice. Surprisingly, the only immune responses detected at 60 h postinfection occurred in the susceptible mice and only upon stimulation of cells from lymph nodes draining the inoculation site with infective larva extract: massive production of interleukin-6 (IL-6) and IL-5 (the latter cytokine was previously suspected to have an effect on L. sigmodontis growth). However, between days 10 and 30 postinfection, extraordinarily high levels of type 1 and type 2 cytokines and expansion of pleural leukocyte infiltration were seen in the resistant C57BL/6 mice, explaining the destruction of worms later. Our results suggest that events early in the infection determine susceptibility or resistance to subsequent microfilarial production and a parasite strategy to use specific immune responses to its own benefit.


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