DDT inhibits the functional activation of murine macrophages and decreases resistance to infection by Mycobacterium microti

G, Marı́a Andrea Nuñez; Estrada, Iris; Calderón-Aranda, Emma S.

doi:10.1016/s0300-483x(02)00078-1

Cited by 23 publications

(6 citation statements)

References 23 publications

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“…Extensive animal evidence suggests several plausible pathways for developmental immunotoxic effects of DDT/E; however, human studies are scarce. In animal studies, postnatal exposure to DDT/E and pyrethroids has been shown to inhibit macrophage activity, response to bacterial infection ( Nuñez et al. 2002 ), and leukocyte proliferation and to increase apoptosis ( Misumi et al.…”

Section: Discussionmentioning

confidence: 99%

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Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort

Huang

Eskenazi

Bornman

et al. 2018

Environ Health Perspect

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Background:Indoor residual spraying (IRS) of insecticides, conducted in low- and middle-income countries to control malaria, may result in high exposure to dichlorodiphenyltrichloroethane (DDT), its breakdown product dichlorodiphenyldichloroethylene (DDE), or pyrethroids. Animal studies suggest in utero exposure to these chemicals may increase childhood infection frequency.Objectives:We investigated associations between maternal DDT/E and pyrethroid metabolite concentration and child infection associations in an IRS setting in which susceptibility factors are common and infections are leading causes of child morbidity and mortality.Methods:Using gas chromatography–mass spectrometry, we measured serum DDT/E and urinary pyrethroid metabolite concentrations in peripartum samples from 674 women participating in the Venda Health Examination of Mother, Babies and their Environment (VHEMBE) study. Counts of persistent child fevers, otitis media, and severe sore throat between 1 and 2 y of age were ascertained from maternal interviews. Associations between DDT/E and pyrethroid metabolite concentrations and infections were estimated using zero-inflated Poisson regression. We estimated relative excess risks due to interaction (RERI) with poverty, maternal energy intake, and maternal HIV status.Results:Concentrations of DDT/E, particularly p,p′-DDE, were associated with higher rates of persistent fevers [IRR=1.21 (95% CI: 1.01, 1.46)], for a 10-fold increase in p,p′-DDE). This association was stronger among children from households below versus above the South African food poverty line [IRR=1.31 (95% CI: 1.08, 1.59) vs. IRR=0.93 (95% CI: 0.69, 1.25), respectively] and for children whose mothers had insufficient versus sufficient caloric intake during pregnancy [IRR=1.30 (95% CI: 1.07, 1.58) vs. IRR=0.96 (95% CI: 0.72, 1.28), respectively].Conclusions:In utero IRS insecticide exposure may increase childhood infection rates. This was particularly apparent among children from poorer households or whose mothers had low energy intake during pregnancy. https://doi.org/10.1289/EHP2657

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Section: Discussionmentioning

confidence: 99%

“…2005 ; ATSDR 2002 , 2003 ; Brander et al. 2016 ) and to specifically increase susceptibility to infection ( Nuñez et al. 2002 ; Suwanchaichinda et al.…”

Section: Introductionmentioning

confidence: 99%

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort

Huang

Eskenazi

Bornman

et al. 2018

Environ Health Perspect

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“…The p,p ′- and o,p ′- isomers of DDT and its primary transformation products DDE and DDD were identified in the dolphin blubber, all of which were confirmed with authentic standards. These compounds have been the primary focus of monitoring − because they are persistent and bioaccumulative in wildlife and have been shown to exhibit toxicity. − The major transformation products are formed under both aerobic conditions ( p,p ′-DDE) and anaerobic conditions ( p,p ′-DDD) . The reductive dechlorination product of DDE, DDMU, was also detected in the blubber ( p,p ′-DDMU was confirmed by authentic standard; 2 other isomers were also detected) .…”

Section: Results and Discussionmentioning

confidence: 99%

Newly Identified DDT-Related Compounds Accumulating in Southern California Bottlenose Dolphins

Mackintosh

Dodder

Shaul

et al. 2016

Environ. Sci. Technol.

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Nontargeted GC×GC-TOF/MS analysis of blubber from 8 common bottlenose dolphins (Tursiops truncatus) inhabiting the Southern California Bight was performed to identify novel, bioaccumulative DDT-related compounds and to determine their abundance relative to the commonly studied DDT-related compounds. We identified 45 bioaccumulative DDT-related compounds of which the majority (80%) is not typically monitored in environmental media. Identified compounds include transformation products, technical mixture impurities such as tris(chlorophenyl)methane (TCPM), the presumed TCPM metabolite tris(chlorophenyl)methanol (TCPMOH), and structurally related compounds with unknown sources, such as hexa- to octachlorinated diphenylethene. To investigate impurities in pesticide mixtures as possible sources of these compounds, we analyzed technical DDT, the primary source of historical contamination in the region, and technical Dicofol, a current use pesticide that contains DDT-related compounds. The technical mixtures contained only 33% of the compounds identified in the blubber, suggesting that transformation products contribute to the majority of the load of DDT-related contaminants in these sentinels of ocean health. Quantitative analysis revealed that TCPM was the second most abundant compound class detected in the blubber, following DDE, and TCPMOH loads were greater than DDT. QSPR estimates verified 4,4',4″-TCPM and 4,4'4,″-TCPMOH are persistent and bioaccumulative.

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“…Indeed, mitochondrial ROS were shown in both mice cells and human cells to activate NF-κB transcription factors ( Chandel et al 2000 , Nemoto et al 2000 , Sena and Chandel 2012 ), suggesting that the constitutively decreased expression of Dif and Rel in 91-R could potentially be adaptive by priming cells for xenobiotic exposures, even in the absence of ROS. In addition, organochlorine insecticides, such as DDT, cause immune dysregulation (reviewed by Corsini et al 2013 ), and DDT and DDE are immunosuppressive in rats, mice, and humans ( Gabliks et al 1975 ; Banerjee 1987a , b ; Rehana and Rao 1992 ; Banerjee et al 1997 ; Nuñez et al 2002 ; Cooper et al 2004 ). A state of readiness was predicted for cells with increased expression of transcripts involved in immune response among larvae resistant to Bacillus thuringiensis toxins ( Dubovskiy et al 2016 ), suggesting that the upregulation of immune response- or apoptosis-related genes may be adaptive with respect to survival when exposed to xenobiotics.…”

Section: Discussionmentioning

confidence: 99%

Variation in Mitochondria-Derived Transcript Levels Associated With DDT Resistance in the91-RStrain ofDrosophila melanogaster(Diptera: Drosophilidae)

Steele

Coates

Seong

et al. 2018

Journal of Insect Science

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The organochloride insecticide dichlorodiphenyltrichloroethane (DDT) and its metabolites can increase cellular levels of reactive oxygen species (ROS), cause mitochondrial dysfunction, and induce apoptosis. The highly DDT-resistant Drosophila melanogaster Meigen 1830 (Drosophila) strain, 91-R, and its susceptible control, 91-C, were used to investigate functional and structural changes among mitochondrial-derived pathways. Resequencing of mitochondrial genomes (mitogenomes) detected no structural differences between 91-R and 91-C, whereas RNA-seq suggested the differential expression of 221 mitochondrial-associated genes. Reverse transcriptase-quantitative PCR validation of 33 candidates confirmed that transcripts for six genes (Cyp12d1-p, Cyp12a4, cyt-c-d, COX5BL, COX7AL, CG17140) were significantly upregulated and two genes (Dif, Rel) were significantly downregulated in 91-R. Among the upregulated genes, four genes are duplicated within the reference genome (cyt-c-d, CG17140, COX5BL, and COX7AL). The predicted functions of the differentially expressed genes, or known functions of closely related genes, suggest that 91-R utilizes existing ROS regulation pathways of the mitochondria to combat increased ROS levels from exposure to DDT. This study represents, to our knowledge, the initial investigation of mitochondrial genome sequence variants and functional adaptations in responses to intense DDT selection and provides insights into potential adaptations of ROS management associated with DDT selection in Drosophila.

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DDT inhibits the functional activation of murine macrophages and decreases resistance to infection by Mycobacterium microti

Cited by 23 publications

References 23 publications

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort

Newly Identified DDT-Related Compounds Accumulating in Southern California Bottlenose Dolphins

Variation in Mitochondria-Derived Transcript Levels Associated With DDT Resistance in the91-RStrain ofDrosophila melanogaster(Diptera: Drosophilidae)

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