Dataset Information

CD14 influences host immune responses and alternative activation of macrophages during Schistosoma mansoni infection.

ABSTRACT: Antigen-presenting cell (APC) plasticity is critical for controlling inflammation in metabolic diseases and infections. The roles that pattern recognition receptors (PRRs) play in regulating APC phenotypes are just now being defined. We evaluated the expression of PRRs on APCs in mice infected with the helminth parasite Schistosoma mansoni and observed an upregulation of CD14 expression on macrophages. Schistosome-infected Cd14(-/-) mice showed significantly increased alternative activation of (M2) macrophages in the livers compared to infected wild-type (wt) mice. In addition, splenocytes from infected Cd14(-/-) mice exhibited increased production of CD4(+)-specific interleukin-4 (IL-4), IL-5, and IL-13 and CD4(+)Foxp3(+)IL-10(+) regulatory T cells compared to cells from infected wt mice. S. mansoni-infected Cd14(-/-) mice also presented with smaller liver egg granulomas associated with increased collagen deposition compared to granulomas in infected wt mice. The highest expression of CD14 was found on liver macrophages in infected mice. To determine if the Cd14(-/-) phenotype was in part due to increased M2 macrophages, we adoptively transferred wt macrophages into Cd14(-/-) mice and normalized the M2 and CD4(+) Th cell balance close to that observed in infected wt mice. Finally, we demonstrated that CD14 regulates STAT6 activation, as Cd14(-/-) mice had increased STAT6 activation in vivo, suggesting that lack of CD14 impacts the IL-4R?-STAT6 pathway, altering macrophage polarization during parasite infection. Collectively, these data identify a previously unrecognized role for CD14 in regulating macrophage plasticity and CD4(+) T cell biasing during helminth infection.

SUBMITTER: Tundup S

PROVIDER: S-EPMC4136223 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD14 influences host immune responses and alternative activation of macrophages during Schistosoma mansoni infection.

Tundup Smanla S Srivastava Leena L Nagy Tamas T Harn Donald D

Infection and immunity 20140527 8

Antigen-presenting cell (APC) plasticity is critical for controlling inflammation in metabolic diseases and infections. The roles that pattern recognition receptors (PRRs) play in regulating APC phenotypes are just now being defined. We evaluated the expression of PRRs on APCs in mice infected with the helminth parasite Schistosoma mansoni and observed an upregulation of CD14 expression on macrophages. Schistosome-infected Cd14(-/-) mice showed significantly increased alternative activation of ( ...[more]

PMID: 24866794

Similar Datasets

Project description:BACKGROUND:Intestinal schistosomiasis due to Schistosoma mansoni was mapped in Cameroon in the 1990s and preventive chemotherapy launched since 2005. A situation analysis conducted in 2011 revealed an increase in schistosomiasis transmission, especially in the equatorial part of the country, despite the fact that Biomphalaria pfeifferi, the main intermediate host of this parasite, is now scarce in many foci. Biomphalaria camerunensis, restricted to the equatorial part of the country, is considered as a less suitable host for S. mansoni due to it resistance to the parasite, although exhibiting a better survival than B. pfeifferi. In a context where human migration is quite frequent as a consequence of terrorism, war in neighboring countries, as well as development of hydraulic projects, it seems appropriate to evaluate the current epidemiological role of B. camerunensis to estimate the risk of extension of S. mansoni distribution in Cameroon. To do this, the susceptibility of three B. pfeifferi and five B. camerunensis populations to a strain of S. mansoni was assessed. Juvenile snails (G1) of each population were infected with S. mansoni miracidia, and prepatent period, infection and survival rates of infected snails, as well as cercarial production were recorded and compared between snail species and populations. RESULTS:Compatibility tests were performed on a total of 827 snails: 344 B. pfeifferi and 483 B. camerunensis. Infection rates were quite heterogeneous, higher in B. pfeifferi (61.5%) as compared to B. camerunensis (7.8%) (Chi-square test: χ2 = 258.88, df = 1, P < 0.0001). All the three B. pfeifferi-infected populations were susceptible to S. mansoni. However, among the five B. camerunensis populations tested, four were susceptible to S. mansoni, with 21.9% as the highest infection rate. The prepatent period was, on average, shorter in B. pfeifferi than in B. camerunensis (P < 0.0001), but the cercarial production was significantly higher in B. camerunensis as compared to B. pfeifferi (P < 0.001). CONCLUSION:These findings indicate that B. camerunensis populations might substantially contribute to S. mansoni transmission and dissemination in Cameroon, their low susceptibility being compensated by their high cercariae production. More attention and surveillance towards this species are required to achieve intestinal schistosomiasis elimination in Cameroon.

Dataset Information

CD14 influences host immune responses and alternative activation of macrophages during Schistosoma mansoni infection.

Publications

CD14 influences host immune responses and alternative activation of macrophages during Schistosoma mansoni infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets