Table 1 Examples of protective and pathogenic effects mediated by innate responses at different stages of acute and early HIV-1 infection

HIV transmission

SLPI, Elafin and defensins help to block HIV infection

SEVI and WFDC-1 enhance HIV infection

Establishment of initial foci of infection

Langerhans cells capture and destroy HIV virions

Type 1 IFNs block HIV replication via upregulation of APOBECs and restriction factors

cDCs and macrophages act as sites for HIV replication and attract plus transmit infection to CD4+ T cells

Local production of pro-inflammatory cytokines drives immune activation, enhancing viral replication

Local virus replication and spread to draining lymph nodes

Type 1 IFNs continue to limit HIV replication

Locally-recruited innate effector cells combat virus replication

Proinflammatory cytokines, type 1 IFNs and WFDC-1 promote local immune activation, enhancing virus replication

DC-SIGN+ DCs carry HIV to lymph nodes and infect CD4+ T cells

Further viral amplification and systemic dissemination

DCs activate innate effector cells including NK and NKT cells and begin to induce HIV-specific T cell responses

NK, NKT and other innate effector cells combat HIV replication

cDCs and macrophages promote HIV transmission to CD4+ T cells

DCs preferentially infect HIV-specific CD4+ T cells

Immune activation mediated by pDCs and cDCs enhances HIV replication

Exponential virus growth and depletion of central memory CD4+ T cells

HIV replication is combated by type 1 IFNs, NK and NKT cells

DCs promote induction of adaptive responses

Immune activation mediated by DCs, NK cells and NKT cells enhances HIV replication

Ongoing virus replication

Soluble innate factors and NK cells contribute to control of virus replication

DCs help to sustain adaptive responses

cDCs and macrophages continue to promote HIV transmission to CD4+ T cells

Immune activation mediated by DCs, NK cells and NKT cells enhances HIV replication