Intestinal helminth co-infection has a negative impact on both anti-Mycobacterium tuberculosis immunity and clinical response to tuberculosis therapy

Abstract

SummaryThe impact of intestinal helminth infection on Mycobacterium tuberculosis (MTB)-specific immune responses during active tuberculosis (TB) is not known. We investigated the role of intestinal helminth infection in anti-MTB immunity by evaluating both cellular phenotype and cytokine profiles in patients with TB and patients with concomitant TB and intestinal helminth infection (TB + Helm) during TB therapy. Twenty-seven per cent of TB patients enrolled for the study were co-infected with at least one intestinal helminth. At baseline, absolute frequencies of leucocytes, monocytes and eosinophils from TB and TB + Helm patients differed from healthy subjects. Concomitant intestinal helminth infection in TB + Helm patients had a negative impact (P < 0·05) on absolute frequencies of CD3 + , CD4 natural killer (NK) T and CD4+ CD25 high T cell subsets when compared to either TB patients or healthy controls. Differences in CD4 + T cell frequencies were accompanied by lower interferon (IFN)-g and elevated and sustained interleukin (IL)-10 levels in whole blood (WB) cultures from TB + Helm compared to TB patients. In addition to a depressed anti-MTB immunity, TB + Helm patients also presented with more severe radiological pulmonary disease, with a significant difference (P = 0·013) in the number of involved lung zones at the end of TB treatment. The above data may indicate that concomitant intestinal helminth infection in patients with newly diagnosed TB skews their cytokine profile toward a T helper 2 response, which could favour persistent MTB infection and a more protracted clinical course of the disease.

Effect of helminth-induced immunity on infections with microbial pathogens

“…Another study also found a higher frequency of helminth infection in patients with pulmonary tuberculosis than in a control group matched by age, sex and neighborhood 19 . A lower IFN-γ response and greater IL-10 response has also been observed in mycobacteria-stimulated whole-blood cultures from helminth-coinfected patients with tuberculosis than in those from patients with tuberculosis 20 . A similar reduction in the production of antigen-specific IFN-γ has also been seen in peripheral blood mononuclear cells from helminth-infected children with responsiveness to bacillus Calmette-Guerin (BCG).…”

Neither Primary nor Memory Immunity to Mycobacterium tuberculosis Infection Is Compromised in Mice with Chronic Enteric Helminth Infection

“…Contrasting the above reports, several other studies have demonstrated that helminth coinfection has a negative impact on the outcome of M. tuberculosis infection. The IFN-␥ response is reduced in helminth-coinfected TB patients (34) and latently infected individuals (35). Several murine studies have shown that there is a poor cellular response to mycobacterial antigens in helminth-coinfected animals (36)(37)(38).…”

Bystander Chronic Infection Negatively Impacts Development of CD8+ T Cell Memory

“…However, accumulating epidemiological evidence suggests that many chronic infections can increase susceptibility and pathology induced by unrelated pathogens. For example, intestinal helminth infections enhance Mycobacterium tuberculosis (Mtb)-induced pulmonary pathology (Resende Co et al, 2007) and increase the risk of developing chronic disease upon hepatitis C virus (HCV) infection (Kamal et al, 2001). Mathematical models indicate that malaria actively contributes to the increased rate of infection with human immunodeficiency virus (HIV) (Abu-Raddad et al, 2006), suggesting that dysregulated immunity due to a bystander chronic infection may be responsible for the increased incidence of other infections.…”