Trends in Immunology
ReviewTo B or not to B: B cells and the Th2-type immune response to helminths
Section snippets
Helminths and the host response
Chronic infection with helminth parasites has a significant impact on global health; more than 2 billion people worldwide are infected, and these parasites can cause high morbidity including malnourishment and anemia. Although drug treatments do exist, reinfection can occur after treatment; typically in parasite endemic areas, and drug resistance is also becoming an issue. As such, the development of effective vaccines against helminths would be a major advance for control and treatment of
Vaccination against helminths
Current strategies to control helminth-related morbidity involve regular and mass drug administration, integrated with disease control through improved sanitation and hygiene [2]. Although safe and effective drugs are currently available for the bulk of human parasitic helminth infections, rapid reinfection and the dramatic rise in drug-resistant helminths of veterinary importance have raised concerns over the feasibility of drug administration as a long-term control strategy [2]. Yet, there is
A protective role for antibodies?
During helminth infection, polarized Th2-type responses promote B cell class switching to IgE and IgG1. Interleukin (IL)-4 receptor signaling and cognate T–B cell interactions mediate production of both isotypes. IgE potently activates mast cells and basophils, on which, antigen crosslinks Fc epsilon Receptor 1 (FcɛRI)-bound IgE to trigger degranulation and release of soluble mediators from these cells (Figure 1). IgE does not play an essential role in protective immunity against
Helminth-induced production of polyclonal antibodies: help or hindrance?
Helminth infection has long been associated with the marked production of polyclonal IgE antibodies. Formal proof that helminth infection can lead to the production of irrelevant antibody specificities has been provided by H. polygyrus bakeri infection of TgH(VI10)xYEN mice [8]. Almost all B cells in these mice express a neutralizing immunoglobulin against the vesicular stomatitis virus glycoprotein (VSV-GP). In these mice, the immunoglobulin heavy chain locus can undergo class switch
Do B cells enhance Th2-type responses
B cells have several important activities in addition to antibody production, including antigen presentation, co-stimulatory molecule signaling, and cytokine production. However, the importance of B cells in driving a T cell-dependent response can vary with the particular antigen and the type of immune microenvironment. In draining lymph nodes, antigen-presenting DCs first interact with naïve T cells in the T zone, and activated T cells then migrate to the B zone 60, 61. In the T:B zone [62],
Helminth-induced regulatory B cells
Immune regulation by B cells was first recognized for autoimmune conditions (Box 2). Regulatory B cells also play a role during helminth infection. B cell deficiency results in enhanced Th2-dependent immunopathology following experimental S. mansoni infection. A similar increase in immune pathology is observed in mice deficient for FcγRs, which indicates a complex relationship between antibody secretion and B cell function in this model [74]. Regulatory B cells also play a role during
Concluding remarks
It is clear that B cells are important in protective immunity against helminths. However, their significance and function can differ greatly depending on the specific parasite. During mucosal responses to helminths, where B cells are essential for protective immunity, antibody secretion appears most significant, and exogenous antibody administration can largely substitute for B cell deficiency. Other helminths elicit host protective responses in the absence of B cells, although even in these
Acknowledgments
N.Harris is supported by the Swiss Vaccine Research Institute. W.C. Gause is supported by NIH grants R01AI66188, R01AI031678, and R01AI069395.
References (95)
Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm
Lancet
(2006)Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection
Cell Host Microbe.
(2008)Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus
Immunity
(2009)Vaccination against cestode parasites: anti-helminth vaccines that work and why
Vet. Parasitol.
(2003)Passive transfer of immunity with serum in mice infected with Nematospiroides dubius: influence of quality and quantity of immune serum
Int. J. Parasitol.
(1982)Induction of resistance against Schistosoma mansoni infection by passive transfer of an IgG2a monoclonal antibody
Vaccine
(1999)Characterisation of effector mechanisms at the host:parasite interface during the immune response to tissue-dwelling intestinal nematode parasites
Int. J. Parasitol.
(2009)Infection with parasitic nematodes confounds vaccination efficacy
Vet. Parasitol.
(2007)Ascaris suum infection negatively affects the response to a Mycoplasma hyopneumoniae vaccination and subsequent challenge infection in pigs
Vaccine
(2009)- et al.
Suppression of the immune response to diphtheria toxoid in murine schistosomiasis
Vaccine
(1997)
Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine, but not irradiated sporozoites, in mice
Vaccine
Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity
Immunity
Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection
J. Allergy Clin. Immunol.
Vaccination with recombinant Ascaris suum 24-kilodalton antigen induces a Th1/Th2-mixed type immune response and confers high levels of protection against challenged Ascaris suum lung-stage infection in BALB/c mice
Int. J. Parasitol.
The SCID but not the RAG-2 gene product is required for S mu-S epsilon heavy chain class switching
Immunity
Helminth infections: the great neglected tropical diseases
J. Clin. Invest.
Vaccination against helminth parasites – the ultimate challenge for vaccinologists?
Immunol. Rev.
Cestode vaccines: origins, current status and future prospects
Parasitology
Hookworm vaccines
Clin. Infect. Dis.
Current status of vaccines for schistosomiasis
Clin. Microbiol. Rev.
Molecular evidence that Heligmosomoides polygyrus from laboratory mice and wood mice are separate species
Parasitology
Protective immunity and eosinophilia in IgE-deficient SJA/9 mice infected with Nippostrongylus brasiliensis and Trichinella spiralis
Proc. Natl. Acad. Sci. U. S. A.
Schistosoma mansoni infection in IgE-producing and IgE-deficient mice
J. Parasitol.
The in vivo role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice
Parasite Immunol.
Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice
Infect. Immun.
Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites
Nature
IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis
J. Immunol.
B-cell deficiency suppresses vaccine-induced protection against murine filariasis but does not increase the recovery rate for primary infection
Infect. Immun.
Radiation-attenuated schistosome vaccination – a brief historical perspective
Parasitology
B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris
Infect. Immun.
B cells have distinct roles in host protection against different nematode parasites
J. Immunol.
Critical role for IgM in host protection in experimental filarial infection
J. Immunol.
Antibody-dependent reductions in mouse hookworm burden after vaccination with Ancylostoma caninum secreted protein 1
J. Infect. Dis.
Immune mechanisms to Ascaris suum in inbred guinea-pigs. I. Passive transfer of immunity by cells or serum
Immunology
Protective role of immunoglobulin G in immunity to Strongyloides ratti
J. Parasitol.
Antibodies to surface epitopes of the carbohydrate larval antigen CarLA are associated with passive protection in strongylid nematode challenge infections
Parasite Immunol.
Expulsion of Nematospiroides dubius from the intestine of mice treated with immune serum
Parasite Immunol.
Transfer of immunity to Nematospiroides dubius: co-operation between lymphoid cells and antibodies in mediating worm expulsion
Parasite Immunol.
Passive protection against fasciolosis in mice by immunization with a monoclonal antibody (ES-78 MoAb)
Parasite Immunol.
Characterization of a monoclonal antibody against infective larvae of Brugia malayi
Immunology
Antibodies to tyvelose exhibit multiple modes of interference with the epithelial niche of Trichinella spiralis
Infect. Immun.
Protection against Trichinella spiralis induced by a monoclonal antibody that promotes killing of newborn larvae by granulocytes
Parasite Immunol.
Glycans as targets for monoclonal antibodies that protect rats against Trichinella spiralis
Glycobiology
Impeded establishment of the infective stage of Trichinella in the intestinal mucosa of mice by passive transfer of an IgA monoclonal antibody
J. Vet. Med. Sci.
Monoclonal IgA antibody-mediated expulsion of Trichinella from the intestine of mice
Parasitology
Characterization of the immune mediator of rapid expulsion of Trichinella spiralis in suckling rats
Immunology
Mechanisms of neonatal mucosal antibody protection
J. Immunol.
Cited by (133)
The protective immunity induced by Trichinella spiralis galectin against larval challenge and the potential of galactomannan as a novel adjuvant
2023, Research in Veterinary ScienceInitiation of type 2 immunity at barrier surfaces
2023, Mucosal ImmunologyAcetate, a metabolic product of Heligmosomoides polygyrus, facilitates intestinal epithelial barrier breakdown in a FFAR2-dependent manner
2022, International Journal for ParasitologyCitation Excerpt :Chronic soil-transmitted helminth infections remain an immense global health problem and although not fatal, they are associated with high morbidity rates, caused by chronic infections often leading to anemia and malnourishment in both humans and livestock (de Silva et al., 2003). Here, we used Heligmosomoides polygyrus as a natural mouse helminth model organism, to explore general mechanisms of initial host tissue invasion before the well-studied immune evasion mechanisms come into play (Behnke et al., 2009; Harris and Gause, 2011; Reynolds et al., 2012; Harris et al., 2014). Of note, helminth infections are different from other pathogen encounters as a simple measure of their size that is significantly larger than bacteria, fungi and viruses or classical host immune cells.
Vaccination with a DNase II recombinant protein against Trichinella spiralis infection in pigs
2021, Veterinary ParasitologyRemote regulation of type 2 immunity by intestinal parasites
2021, Seminars in Immunology