Coexistent Helminth Infection–Mediated Modulation of Chemokine Responses in Latent Tuberculosis

Abstract Coexistent helminth infections are known to modulate T cell and cytokine responses in latent infection with Mycobacterium tuberculosis. However, their role in modulating chemokine responses in latent tuberculosis (LTB) has not been explored. Because chemokines play a vital role in the protective immune responses in LTB, we postulated that coexistent helminth infection could modulate chemokine production in helminth-LTB coinfection. To test this, we measured the levels of a panel of CC and CXC chemokines at baseline and following mycobacterial Ag or mitogen stimulation in individuals with LTB with (Strongyloides stercoralis+LTB+) or without S. stercoralis (S. stercoralis−LTB+) infection and in individuals without both infections, healthy controls (HC). At baseline (in the absence of a stimulus), S. stercoralis+LTB+ individuals exhibited significantly diminished production of CCL1, CCL2, CCL4, CCL11, CXCL9, CXCL10, and CXCL11 in comparison with S. stercoralis−LTB+ and/or HC individuals. Upon mycobacterial Ag stimulation, S. stercoralis+LTB+ individuals exhibited significantly diminished production of CCL1, CCL2, CCL4, CCL11, CXCL2, CXCL9, and CXCL10 in comparison with S. stercoralis−LTB+ and/or HC individuals. No differences were observed upon mitogen stimulation. Finally, after anthelmintic treatment, the baseline levels of CCL1, CCL2, CCL4, CCL11, and CXCL11 and mycobacterial Ag–stimulated levels of CCL1, CCL2, CCL11, CXCL2, and CXCL10 were significantly increased in S. stercoralis+LTB+ individuals. Thus, our data demonstrate that S. stercoralis+LTB+ individuals are associated with a compromised ability to express both CC and CXC chemokines and that this defect is at least partially reversible upon treatment. Hence, coexistent helminth infection induces downmodulation of chemokine responses in LTB individuals with likely potential effects on tuberculosis pathogenesis.