Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome

Abstract Clostridium difficile (reclassified as “Clostridioides”) is the leading cause of hospital-acquired infections in the United States, and is associated with high-patient mortality and high rates of recurrence. Inflammasome priming and activation by the bacterial toxins, TcdA, TcdB, and C. difficile transferase (CDT), initiates a potent immune response that is characterized by interleukin- (IL) 8, IL-1β, and neutrophil recruitment, and is required for pathogen killing. However, it is becoming clearer that a strong inflammatory response during C. difficile infection can result in host tissue damage, and is associated with worse patient outcome. Recent work has begun to show that a type-2 immune response, most often associated with helminth infections, allergy, and asthma, may be protective during C. difficile infection. While the mechanisms through how this response protect are still unclear, there is evidence that it is mediated through eosinophil activity. This chapter will review the immune response to C. difficile, how the inflammasome signaling during infection can deleterious to the host, as well as the current understanding of a protective type-2 immunity. Understanding the host immune response may help to provide insight into novel approaches to prognosis markers, as well as how treat patient C. difficile infection without, or in addition to, antibiotics.

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A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization

Cell ◽

10.1016/j.cell.2021.02.046 ◽

2021 ◽

Author(s):

Mark R. Cronan ◽

Erika J. Hughes ◽

W. Jared Brewer ◽

Gopinath Viswanathan ◽

Emily G. Hunt ◽

...

Keyword(s):

Immune Response ◽

Granuloma Formation ◽

Type 2 Immune Response ◽

Tuberculous Granuloma ◽

Canonical Type

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Dairy Heifers Naturally Exposed toFasciola hepaticaDevelop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation

Infection and Immunity ◽

10.1128/iai.00607-17 ◽

2017 ◽

Vol 86 (1) ◽

Cited By ~ 3

Author(s):

John Graham-Brown ◽

Catherine Hartley ◽

Helen Clough ◽

Aras Kadioglu ◽

Matthew Baylis ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Peripheral Blood ◽

Serum Antibody ◽

Enzyme Linked Immunosorbent Assay ◽

Mixed Effect ◽

Content Type ◽

Grazing Season ◽

Type 2 Immune Response

ABSTRACTFasciola hepaticais a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response toF. hepaticafollowing natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed toF. hepaticainfection. Cohorts of replacement dairy heifer calves (n= 42) with no prior exposure toF. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through anF. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-γ) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge withF. hepatica. This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.

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Macrophage-Derived Osteopontin Influences the Amplification of Cryptococcus neoformans–Promoting Type 2 Immune Response

The Journal of Immunology ◽

10.4049/jimmunol.2100202 ◽

2021 ◽

pp. ji2100202

Author(s):

Adithap Hansakon ◽

Chin Wen Png ◽

Yongliang Zhang ◽

Pornpimon Angkasekwinai

Keyword(s):

Immune Response ◽

Cryptococcus Neoformans ◽

Type 2 Immune Response

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Erratum for Graham-Brown et al., “Dairy Heifers Naturally Exposed to Fasciola hepatica Develop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation”

Infection and Immunity ◽

10.1128/iai.00247-18 ◽

2018 ◽

Vol 86 (6) ◽

Cited By ~ 2

Author(s):

John Graham-Brown ◽

Catherine Hartley ◽

Helen Clough ◽

Aras Kadioglu ◽

Matthew Baylis ◽

...

Keyword(s):

Immune Response ◽

Fasciola Hepatica ◽

Dairy Heifers ◽

Type 2 Immune Response

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NK cell recruitment limits tissue damage during an enteric helminth infection

Mucosal Immunology ◽

10.1038/s41385-019-0231-8 ◽

2019 ◽

Vol 13 (2) ◽

pp. 357-370 ◽

Cited By ~ 2

Author(s):

Maria E. Gentile ◽

Yue Li ◽

Amicha Robertson ◽

Kathleen Shah ◽

Ghislaine Fontes ◽

...

Keyword(s):

Immune Response ◽

Nk Cells ◽

Helminth Infection ◽

Nk Cell ◽

Early Response ◽

Cell Recruitment ◽

Parasitic Helminths ◽

Cxcr3 Expression ◽

Type 2 Immune Response

AbstractParasitic helminths cause significant damage as they migrate through host tissues to complete their life cycle. While chronic helminth infections are characterized by a well-described Type 2 immune response, the early, tissue-invasive stages are not well understood. Here we investigate the immune pathways activated during the early stages of Heligmosomoides polygyrus bakeri (Hpb), a natural parasitic roundworm of mice. In contrast to the Type 2 immune response present at later stages of infection, a robust Type 1 immune signature including IFNg production was dominant at the time of parasite invasion and granuloma formation. This early response was associated with an accumulation of activated Natural Killer (NK) cells, with no increase of other innate lymphoid cell populations. Parabiosis and confocal microscopy studies indicated that NK cells were recruited from circulation to the small intestine, where they surrounded parasitic larvae. NK cell recruitment required IFNγ receptor signaling, but was independent of CXCR3 expression. The depletion of tissue-infiltrating NK cells altered neither worm burden nor parasite fitness, but increased vascular injury, suggesting a role for NK cells in mediating tissue protection. Together, these data identify an unexpected role for NK cells in promoting disease tolerance during the invasive stage of an enteric helminth infection.

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