Carbon nanotubes (CNTs) are increasingly being developed for use in biomedical applications, including
drug delivery. One of the most promising applications under evaluation is in treating pulmonary diseases
such as tuberculosis. Once inhaled or administered, the nanoparticles are likely to be recognised by innate
immune molecules in the lungs such as hydrophilic pulmonary surfactant proteins. Here, we set out to
examine the interaction between surfactant protein D (SP-D), a key lung pattern recognition molecule and
CNTs, and possible downstream effects on the immune response via macrophages. We show here that a
recombinant form of human SP-D (rhSP-D) bound to oxidised and carboxymethyl cellulose (CMC) coated
CNTs via its C-type lectin domain and enhanced phagocytosis by U937 and THP-1 macrophages/monocytic
cell lines, together with an increased pro-inflammatory response, suggesting that sequestration of
SP-D by CNTs in the lungs can trigger an unwanted and damaging immune response. We also observed
that functionalised CNTs, opsonised with rhSP-D, continued to activate complement via the classical
pathway, suggesting that C1q, which is the recognition sub-component of the classical pathway, and SP-D
have distinct pattern recognition sites on the CNTs. Consistent with our earlier reports, complement deposition
on the rhSP-D opsonised CNTs led to dampening of the pro-inflammatory immune response by
THP-1 macrophages, as evident from qPCR, cytokine array and NF-κB nuclear translocation analyses. This
study highlights the importance of understanding the interplay between innate immune humoral factors
including complement in devising nanoparticle based drug delivery strategies.