Chronic Helminth Infection Does Not Exacerbate Mycobacterium Tuberculosis Infection

Overview

Journal PLoS Negl Trop Dis

Specialties Infectious Diseases
Tropical Medicine

Date 2013 Jan 4

PMID 23285308

Citations 28

Authors

Marc P Hubner

Kristin E Killoran

Michael Rajnik

Samuel Wilson

Kevin C Yim

Marina N Torrero

Christopher P Morris

Boris Nikonenko

Jorge C G Blanco

Val G Hemming

Edward Mitre

Affiliations

Soon will be listed here.

Abstract

Background: Chronic helminth infections induce a Th2 immune shift and establish an immunoregulatory milieu. As both of these responses can suppress Th1 immunity, which is necessary for control of Mycobacterium tuberculosis (MTB) infection, we hypothesized that chronic helminth infections may exacerbate the course of MTB.

Methodology/principal Findings: Co-infection studies were conducted in cotton rats as they are the natural host for the filarial nematode Litomosoides sigmodontis and are an excellent model for human MTB. Immunogical responses, histological studies, and quantitative mycobacterial cultures were assessed two months after MTB challenge in cotton rats with and without chronic L. sigmodontis infection. Spleen cell proliferation and interferon gamma production in response to purified protein derivative were similar between co-infected and MTB-only infected animals. In contrast to our hypothesis, MTB loads and occurrence and size of lung granulomas were not increased in co-infected animals.

Conclusions/significance: These findings suggest that chronic filaria infections do not exacerbate MTB infection in the cotton rat model. While these results suggest that filaria eradication programs may not facilitate MTB control, they indicate that it may be possible to develop worm-derived therapies for autoimmune diseases that do not substantially increase the risk for infections.

Citing Articles

Immunological and Haematological Relevance of Helminths and Complex Coinfection among Newly Diagnosed Pulmonary Tuberculosis Patients from Bobo-Dioulasso, Burkina Faso.

Djibougou D, Mensah G, Kabore A, Toe I, Sawadogo L, Lompo P Biomedicines. 2024; 12(7).

PMID: 39062045 PMC: 11274831. DOI: 10.3390/biomedicines12071472.

Intestinal helminth co-infection and associated factors among pulmonary tuberculosis patients in Africa and Asia: a systematic review and meta-analysis.

Zenebe Y, Habtamu M, Abebe M, Tulu B, Atnafu A, Mekonnen D BMC Infect Dis. 2023; 23(1):739.

PMID: 37899439 PMC: 10614413. DOI: 10.1186/s12879-023-08716-9.

Concurrent Infection With the Filarial Helminth Attenuates or Worsens Influenza A Virus Pathogenesis in a Stage-Dependent Manner.

Hardisty G, Knipper J, Fulton A, Hopkins J, Dutia B, Taylor M Front Immunol. 2022; 12:819560.

PMID: 35140712 PMC: 8818685. DOI: 10.3389/fimmu.2021.819560.

Highlighting the Relevance of CD8 T Cells in Filarial Infections.

Kwarteng A, Asiedu E, Koranteng K, Opoku Asiedu S Front Immunol. 2021; 12:714052.

PMID: 34603287 PMC: 8481813. DOI: 10.3389/fimmu.2021.714052.

Protective Effect of Intestinal Helminthiasis Against Tuberculosis Progression Is Abrogated by Intermittent Food Deprivation.

Garrido-Amaro C, Cardona P, Gasso D, Arias L, Velarde R, Tvarijonativiciute A Front Immunol. 2021; 12:627638.

PMID: 33936040 PMC: 8079633. DOI: 10.3389/fimmu.2021.627638.

References

Babu S, Bhat S, Kumar N, Anuradha R, Kumaran P, Gopi P . Attenuation of toll-like receptor expression and function in latent tuberculosis by coexistent filarial infection with restoration following antifilarial chemotherapy. PLoS Negl Trop Dis. 2009; 3(7):e489. PMC: 2710006. DOI: 10.1371/journal.pntd.0000489. View

Potian J, Rafi W, Bhatt K, McBride A, Gause W, Salgame P . Preexisting helminth infection induces inhibition of innate pulmonary anti-tuberculosis defense by engaging the IL-4 receptor pathway. J Exp Med. 2011; 208(9):1863-74. PMC: 3171086. DOI: 10.1084/jem.20091473. View

Elias D, Britton S, Kassu A, Akuffo H . Chronic helminth infections may negatively influence immunity against tuberculosis and other diseases of public health importance. Expert Rev Anti Infect Ther. 2007; 5(3):475-84. DOI: 10.1586/14787210.5.3.475. View

Wilson M, Taylor M, Balic A, Finney C, Lamb J, Maizels R . Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med. 2005; 202(9):1199-212. PMC: 2213237. DOI: 10.1084/jem.20042572. View

Saeftel M, Arndt M, Specht S, Volkmann L, Hoerauf A . Synergism of gamma interferon and interleukin-5 in the control of murine filariasis. Infect Immun. 2003; 71(12):6978-85. PMC: 308906. DOI: 10.1128/IAI.71.12.6978-6985.2003. View

Hubner M, Torrero M, McCall J, Mitre E . Litomosoides sigmodontis: a simple method to infect mice with L3 larvae obtained from the pleural space of recently infected jirds (Meriones unguiculatus). Exp Parasitol. 2009; 123(1):95-8. PMC: 2737475. DOI: 10.1016/j.exppara.2009.05.009. View

Dittrich A, Erbacher A, Specht S, Diesner F, Krokowski M, Avagyan A . Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J Immunol. 2008; 180(3):1792-9. DOI: 10.4049/jimmunol.180.3.1792. View

Wammes L, Hamid F, Wiria A, de Gier B, Sartono E, Maizels R . Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum. Eur J Immunol. 2010; 40(2):437-42. DOI: 10.1002/eji.200939699. View

Erb K, Trujillo C, Fugate M, Moll H . Infection with the helminth Nippostrongylus brasiliensis does not interfere with efficient elimination of Mycobacterium bovis BCG from the lungs of mice. Clin Diagn Lab Immunol. 2002; 9(3):727-30. PMC: 119979. DOI: 10.1128/cdli.9.3.727-730.2002. View

10.

Talaat K, Bonawitz R, Domenech P, Nutman T . Preexposure to live Brugia malayi microfilariae alters the innate response of human dendritic cells to Mycobacterium tuberculosis. J Infect Dis. 2005; 193(2):196-204. DOI: 10.1086/498912. View

11.

Elwood R, Wilson S, Blanco J, Yim K, Pletneva L, Nikonenko B . The American cotton rat: a novel model for pulmonary tuberculosis. Tuberculosis (Edinb). 2006; 87(2):145-54. DOI: 10.1016/j.tube.2006.07.001. View

12.

Hubner M, Torrero M, Mitre E . Type 2 immune-inducing helminth vaccination maintains protective efficacy in the setting of repeated parasite exposures. Vaccine. 2009; 28(7):1746-57. PMC: 3138473. DOI: 10.1016/j.vaccine.2009.12.016. View

13.

van Riet E, Hartgers F, Yazdanbakhsh M . Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology. 2007; 212(6):475-90. DOI: 10.1016/j.imbio.2007.03.009. View

14.

Summers R, Elliott D, Urban Jr J, Thompson R, Weinstock J . Trichuris suis therapy in Crohn's disease. Gut. 2004; 54(1):87-90. PMC: 1774382. DOI: 10.1136/gut.2004.041749. View

15.

Hubner M, Stocker J, Mitre E . Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells. Immunology. 2008; 127(4):512-22. PMC: 2729528. DOI: 10.1111/j.1365-2567.2008.02958.x. View

16.

Babu S, Bhat S, Kumar N, Jayantasri S, Rukmani S, Kumaran P . Human type 1 and 17 responses in latent tuberculosis are modulated by coincident filarial infection through cytotoxic T lymphocyte antigen-4 and programmed death-1. J Infect Dis. 2009; 200(2):288-98. PMC: 2997351. DOI: 10.1086/599797. View

17.

Lipner E, Gopi P, Subramani R, Kolappan C, Sadacharam K, Kumaran P . Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence. Am J Trop Med Hyg. 2006; 74(5):841-7. View

18.

Elias D, Mengistu G, Akuffo H, Britton S . Are intestinal helminths risk factors for developing active tuberculosis?. Trop Med Int Health. 2006; 11(4):551-8. DOI: 10.1111/j.1365-3156.2006.01578.x. View

19.

Dias A, Castro S, Souza Alves C, Rezende A, Rodrigues M, Machado R . Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis. Mem Inst Oswaldo Cruz. 2011; 106(5):617-9. DOI: 10.1590/s0074-02762011000500015. View

20.

Maizels R, Balic A, Gomez-Escobar N, Nair M, Taylor M, Allen J . Helminth parasites--masters of regulation. Immunol Rev. 2004; 201:89-116. DOI: 10.1111/j.0105-2896.2004.00191.x. View