Helminth Coinfection Alters Monocyte Activation, Polarization, and Function in Latent Mycobacterium tuberculosis Infection

Abstract

Helminth infections are known to influence T and B cell responses in latent tuberculosis infection (LTBI). Whether helminth infections also modulate monocyte responses in helminth-LTBI coinfection has not been fully explored. To this end, we examined the activation, polarization, and function of human monocytes isolated from individuals with LTBI with (n = 25) or without (n = 25) coincident Strongyloides stercoralis infection (S. stercoralis-positive and S. stercoralis-negative respectively). Our data reveal that the presence of S. stercoralis infection is associated with lower frequencies of monocytes expressing CD54, CD80, CD86 at baseline (absence of stimulation) and in response to mycobacterial-Ag stimulation than monocytes from S. stercoralis-negative individuals. In contrast, S. stercoralis infection was associated with higher frequencies of M2-like monocytes, as determined by expression of CD206 and CD163. Monocytes from S. stercoralis-positive individuals had a reduced capacity to phagocytose or exhibit respiratory burst activity following mycobacterial-Ag or LPS stimulation and were less capable of expression of IL-1b, TNF-a, IL-6, and IL-12 at baseline and/or following Ag stimulation compared with those without S. stercoralis infection. In addition, definitive treatment of S. stercoralis infection resulted in a significant reversal of the altered monocyte function 6 mo after anthelmintic therapy. Finally, T cells from S. stercoralis-positive individuals exhibited significantly lower activation at baseline or following mycobacterial-Ag stimulation. Therefore, our data highlight the induction of dampened monocyte activation, enhanced M2 polarization, and impaired monocyte function in helminth-LTBI coinfection. Our data also reveal a different mechanism by which helminth infection modulates immune function in LTBI.

Impaired host resistance to Salmonella during helminth co-infection is restored by anthelmintic treatment prior to bacterial challenge

“…Anthelmintic treatment, also known as 'deworming', is the current treatment strategy for helminth infection and needs to be periodically administered to at-risk human and livestock populations. Helminth infection has been associated with impaired host resistance to co-infection with various pathogenic microbes, including bacterial pathogens, both in human populations [2][3][4][5][6] and in mouse models of co-infection [7][8][9][10][11][12][13][14][15][16][17]. However, it is not clear whether anthelmintic treatment is sufficient to restore host resistance to microbial pathogens.…”

Pulmonary insults exacerbate susceptibility to oral Listeria monocytogenes infection through the production of IL-10 by NK cells

“…In humans with latent Mtb and helminth infection, Rajamanickam et al report an overall impairment in monocyte function, with a decrease in phagocytic activity and a shift towards an M2 phenotype, and diminished proinflammatory cytokine production but with an increase in IL-10 production. Interestingly, in this study, when anthelmintic therapy was introduced, a restoration in monocyte activity and pro-inflammatory cytokine production was observed [60]. Thus, coinfections have often been tied to alterations in the immune response through the dampening of myeloid cell activity and the induction of anti-inflammatory responses.…”

Promising Technologies in the Field of Helminth Vaccines

“…For example, blood-fluke Schistosoma becomes more deadly in Egypt where hepatitis C virus is prevalent leading to severe liver disease ( 18 ). Moreover, the nematode Strongyloides was shown to reduce monocyte and T cell activation increasing the pathogenicity of tuberculosis infections ( 19 ), and human T-cell leukemia virus 1 ( 20 ).…”