Immunotoxicity mechanisms of perfluorinated compounds PFOA and PFOS

doi:10.1016/j.chemosphere.2021.132892

Chemosphere

Volume 291, Part 2, March 2022, 132892

https://doi.org/10.1016/j.chemosphere.2021.132892 Get rights and content

Highlights

•
PFOA and PFOS have toxic effects on the immune system of the body.
•
Non-atopic immune responses to PFOA and PFOS were identified.
•
Specific immune responses to PFOA and PFOS were uncovered.
•
Mechanisms of PFOA and PFOS immunotoxicity were summarized.

Abstract

Perfluorinated and polyfluorinated compounds (PFASs) are a class of synthetic chemical substances that are widely used in human production and life, such as fire-fighting foams, textiles and clothing, surfactants, and surface protective agents. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are the most abundant and common perfluorinated compounds in biota and humans. Currently, PFOA and PFOS have been listed in the Stockholm Convention on Persistent Organic Pollutants, and their production has been halted in many countries. However, because the high-energy carbon-fluorine bond can make it resistant to hydrolysis, photolysis, microbial degradation, and vertebrate metabolism, PFOA and PFOS show environmental persistence and bioaccumulation and hence, are of great concern to humans and wildlife. PFOA and PFOS have toxic effects on the immune system of the body. This article reviewed the effects of PFOA and PFOS on immune organs such as the spleen, bone marrow, and thymus of mice and zebrafish, and the effects on non-specific immune functions such as the skin barrier, intestinal mucosal barrier, and humoral immunity. We also reviewed the influence of specific immune functions based on cellular immunity, and further summarized the possible immune toxicity mechanisms such as AIM2 inflammasome activation, gene dysregulation, and signal pathway disorders caused by PFOA and PFOS. The aim of this review was to provide a reference for further understanding of the immunotoxicity and the responsible mechanism of PFOA and PFOS.

Graphical abstract

Introduction

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are perfluorinated organic compounds. Since the 1950s, PFOA and PFOS have been widely used in chemical electroplating, cookware coating, textile manufacturing, food packaging, and other fields because of their excellent stability, extremely low surface tension, and hydrophobic and oleophobic characteristics (Houde et al., 2006; Goosey and Harrad, 2011). In recent years, with the gradual in-depth research on PFOA and PFOS, it has been found that its non-negligible characteristics of non-degradability, strong bioaccumulation, and long-distance migration have attracted widespread attention. PFOA is mainly absorbed by the body through food intake (Lau et al., 2007; Perfluorooctane sulfonate, 2008), and studies have also shown that skin contact is an important way for the human body to come into contact with these chemicals (Mousavi et al., 2021). Studies have found that PFOA and PFOS can be detected in all parts of the human body, including hair, tissues, organs, and secretions, and when the accumulated concentration in the body reaches a certain threshold, it exerts various toxic effects on animals and humans (Pasecnaja et al., 2021). A study on 616 American Red Cross male and female blood donors demonstrated that the plasma PFOS content ranged from 4.3 to 14.5 ng/ml, and the PFOA content ranged from 1.1 to 3.4 ng/ml, which were higher than other measured PFCs (Olsen et al., 2017). Another study conducted in Poland showed that the content of PFOS in the plasma of 429 Polish citizens was 1.61–40.14 ng/ml, and the content of PFOA was 0.67–12.56 ng/ml (Góralczyk et al., 2015).

The immunotoxicity of PFOA and PFOS in animals and humans is mainly due to the immune organs, immune function, and immune cells. However, there are few studies on the immunotoxicity of PFOA and PFOS, which were started late. This article systematically reviews the immunotoxicity of PFOA and PFOS studied in recent years, summarizes the main effects of PFOA and PFOS on immune organs, and the non-atopic immune responses and specific immune responses of animals or humans to PFOA and PFOS. There are several possible mechanisms of PFOA and PFOS immunotoxicity. These provide a reference for exploring more in-depth effects and potential mechanisms.

Section snippets

Spleen

Studies have shown that exposure to PFOS can cause spleen atrophy and dilation of the splenic sinuses (Wang et al., 2011), and exposure to PFOA can also cause spleen atrophy (Wang et al., 2014). In one study, four groups of male BALB/c mice were orally administered 0, 2.5, 5, and 10 mg/kg/day PFOS for three consecutive weeks, and then given a one-week recovery period. The spleens were separated for testing. It is known that the spleen index decreases in a dose-dependent manner; that is, the

Non-specific immunity

PFOA exposure can inhibit the adaptive immune system and affect the resistance of organisms to foreign poisons (Pecquet et al., 2020). However, there are relatively few studies on the influence of PFOA and PFOS on innate immunity. In an experiment using zebrafish embryos to explore the exposure of innate immune cells to PFOA (Pecquet et al., 2020), it was determined that the PFOA concentration that killed 50% (LC50) of zebrafish embryos was 300 mg/L. After 48 h of exposure to PFOA, if the tail

Activation of AIM2 inflammatory small bodies

A study conducted by Wang's group that the activation mechanism of AIM2 inflammatory small bodies plays an important role in PFOS-induced tissue inflammation and injury. This process involves the Ca 2+ -PKC–NF–B/JNK-BAX/BAK-mtDNA-AIM2 axis (Wang et al., 2021). AIM2 is a DNA receptor that identifies the double-stranded DNA of an organism or foreign body, which in turn induces an inflammatory response (Schroder and Tschopp, 2010). The authors found that PFOS exposure significantly increased the

Conclusion

PFOA and PFOS can be accumulated in the body mainly through skin contact and intestinal absorption, and produce immunotoxicity in immune organs such as the spleen, bone marrow, and thymus (Table 1), as well as non-specific and specific immune systems (Table 2). Due to species differences in animals and the uncertainty and inconsistency of research data, research results may be different. At the same time, in the real environment, environmental pollutants PFOA and PFOS are mainly at the

Author contribution

Luyun Liang, Yongling Pan, Lihua Bin, Yu Liu: Methodology, Data collection, Investigation, Writing- Original draft preparation, Wenjun Huang: Writing-revision, Keng Po Lai, Rong Li: Supervision, Conceptualization, Writing- Reviewing and Editing, Funding acquisition.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This study is supported by the College Student Innovation Project (No. 202010601075), National Natural Science Foundation of Guangxi (No. 2019GXNSFBA185015) and National Natural Science Foundation of China (No. 82160282).

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¹: They contributed equally to this work.

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Immunotoxicity mechanisms of perfluorinated compounds PFOA and PFOS

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Spleen

Non-specific immunity

Activation of AIM2 inflammatory small bodies

Conclusion

Author contribution

Declaration of competing interest

Acknowledgements

Environ. Res.

Toxicology

Curr. Opin. Immunol.

Toxicol. Appl. Pharmacol.

Environ. Int.

Sci. Total Environ.

Fish Shellfish Immunol.

Int. J. Hyg Environ. Health

Environ. Int.

Mar. Environ. Res.

Chem. Biol. Interact.

J. Hazard Mater.

Blood

Environ. Res.

Food Chem. Toxicol.

Toxicology

Food Chem. Toxicol.

Cell

Food Chem. Toxicol.

Toxicol. Lett.

Ecotoxicol. Environ. Saf.

Chemosphere

Prenatal Exposure to Perfluoralkyl Substances (PFASs) Associated with Respiratory Tract Infections but Not Allergy- and Asthma-Related Health Outcomes in Childhood

Internal exposure to perfluoroalkyl substances (PFASs) and biological markers in 101 healthy 1-year-old children: associations between levels of perfluorooctanoic acid (PFOA) and vaccine response

Arch. Toxicol.

Environmental perfluorooctane sulfonate exposure drives T cell activation in bottlenose dolphins

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Modulation of Nrf2 by quercetin in doxorubicin-treated rats

Heliyon

DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells

BMC Immunol.

Immunological mechanisms of vaccination

Nat. Immunol.

Notch signalling during peripheral T-cell activation and differentiation

Nat. Rev. Immunol.

Pre-natal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood

J. Immunot.

Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection

Science

Lysosomal cysteine proteases: more than scavengers

Biochim. Biophys. Acta Protein Struct. Mol. Enzymol.

Cell biology of tight junction barrier regulation and mucosal disease

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Nature

Mitochondria and mitophagy: the Yin and Yang of cell death control

Circ. Res.

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Host immune responses to the itch mite, Sarcoptes scabiei, in humans

Parasites Vectors

Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival

J. Immunol.

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Nat. Rev. Immunol.

Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin

J. Toxicol. Environ. Health

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Nat. Rev. Immunol.

The biology of IGE and the basis of allergic disease

Annu. Rev. Immunol.

Serum vaccine antibody concentrations in adolescents exposed to perfluorinated compounds

Environ. Health Perspect.

Subacute dermal toxicity of perfluoroalkyl carboxylic acids: comparison with different carbon-chain lengths in human skin equivalents and systemic effects of perfluoroheptanoic acid in Sprague Dawley rats